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Cell Membrane Structure and Function

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Membranes and Cell TransportMembranes and Cell Transport All cells are surrounded by All cells are surrounded by

a plasma membrane. a plasma membrane. Cell membranes are Cell membranes are

composed of a composed of a lipid bilayerlipid bilayer with globular with globular proteinsproteins embedded in the bilayer.embedded in the bilayer.

On the external surface, On the external surface, carbohydrate groups join carbohydrate groups join with lipids to form with lipids to form glycolipids,glycolipids, and with and with proteins to form proteins to form glycoproteinsglycoproteins. These . These function as cell identity function as cell identity markers.markers.

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Fluid Mosaic Model In 1972, S. Singer and G. Nicolson proposed the In 1972, S. Singer and G. Nicolson proposed the

Fluid Mosaic ModelFluid Mosaic Model of membrane structure of membrane structureExtracellular fluid

CarbohydrateGlycolipid

Transmembraneproteins

Glycoprotein

Peripheralprotein

Cholesterol

Filaments ofcytoskeleton

Cytoplasm

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Phospholipid BilayerPhospholipid Bilayer Mainly 2 layers of Mainly 2 layers of phospholipids; phospholipids; the non-polar tails point the non-polar tails point

inward and the polar heads are on the surface.inward and the polar heads are on the surface. ContainsContains cholesterol cholesterol in animal cells.in animal cells. Is fluid, allowing proteins to move around within the bilayer.Is fluid, allowing proteins to move around within the bilayer.

Polarhydro-philicheads

Nonpolarhydro-phobictails

Polarhydro-philicheads

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PhospholipidsPhospholipids In phospholipids, two of the –OH groups on glycerol are joined In phospholipids, two of the –OH groups on glycerol are joined

to fatty acids. The third –OH joins to a phosphate group which to fatty acids. The third –OH joins to a phosphate group which joins, in turn, to another polar group of atoms. joins, in turn, to another polar group of atoms.

The phosphate and polar groups are hydrophilic (polar head) The phosphate and polar groups are hydrophilic (polar head) while the hydrocarbon chains of the 2 fatty acids are while the hydrocarbon chains of the 2 fatty acids are hydrophobic (nonpolar tails).hydrophobic (nonpolar tails).

Structural formula Space-filling model Phospholipid symbol

Hydrophilichead

Hydrophobictails

Fatty acids

Choline

Phosphate

Glycerol

Hyd

rop

ho

bic

tai

lsH

ydro

ph

i lic

hea

d

6

Membrane ComponentsMembrane Components Membrane carbohydratesMembrane carbohydrates

Interact with the surface molecules of other cells, facilitating cell-cell Interact with the surface molecules of other cells, facilitating cell-cell recognitionrecognition

Cell-cell recognition is a cell’s ability to distinguish one type of Cell-cell recognition is a cell’s ability to distinguish one type of neighboring cell from anotherneighboring cell from another

Steroid CholesterolSteroid Cholesterol Wedged between phospholipid molecules in the plasma membrane of Wedged between phospholipid molecules in the plasma membrane of

animal cells.animal cells. At warm temperatures (such as 37°C), cholesterol restrains the At warm temperatures (such as 37°C), cholesterol restrains the

movement of phospholipids and reduces fluidity.movement of phospholipids and reduces fluidity. At cool temperatures, it maintains fluidity by preventing tight packing.At cool temperatures, it maintains fluidity by preventing tight packing. Thus, cholesterol acts as a “temperature buffer” for the membrane, Thus, cholesterol acts as a “temperature buffer” for the membrane,

resisting changes in membrane fluidity as temperature changes.resisting changes in membrane fluidity as temperature changes.

Cholesterol

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Membrane ComponentsMembrane Components Membrane ProteinsMembrane Proteins

A membrane is a collage of different proteins embedded in the A membrane is a collage of different proteins embedded in the fluid matrix of the lipid bilayerfluid matrix of the lipid bilayer

Peripheral proteins are appendages loosely bound to the Peripheral proteins are appendages loosely bound to the surface of the membranesurface of the membrane

Integral proteins penetrate the hydrophobic core of the lipid Integral proteins penetrate the hydrophobic core of the lipid bilayerbilayer

Many are transmembrane proteins, completely spanning the Many are transmembrane proteins, completely spanning the membranemembrane

Glycoprotein

Carbohydrate

Microfilamentsof cytoskeleton Cholesterol Peripheral

proteinIntegral

protein

Glycolipid

Fibers of extracellularmatrix (ECM)

N-terminus

C-terminus

HelixCYTOPLASMICSIDE

EXTRACELLULARSIDE

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Functions of Cell MembranesFunctions of Cell Membranes

Regulate the passage of substance into Regulate the passage of substance into and out of cells and between cell and out of cells and between cell organelles and cytosolorganelles and cytosol

Detect chemical messengers arriving at Detect chemical messengers arriving at the surfacethe surface

Link adjacent cells together by membrane Link adjacent cells together by membrane junctionsjunctions

Anchor cells to the extracellular matrixAnchor cells to the extracellular matrix

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6 Major Functions Of Membrane Proteins6 Major Functions Of Membrane Proteins

1. Transport. (left) A protein that spans the membrane may provide a hydrophilic channel across the membrane that is selective for a particular solute. (right) Other transport proteins shuttle a substance from one side to the other by changing shape. Some of these proteins hydrolyze ATP as an energy ssource to actively pump substances across the membrane

2. Enzymatic activity. A protein built into the membrane may be an enzyme with its active site exposed to substances in the adjacent solution. In some cases, several enzymes in a membrane are organized as a team that carries out sequential steps of a metabolic pathway.

3. Signal transduction. A membrane protein may have a binding site with a specific shape that fits the shape of a chemical messenger, such as a hormone. The external messenger (signal) may cause a conformational change in the protein (receptor) that relays the message to the inside of the cell.

ATP

Enzymes

Signal

Receptor

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Cell-cell recognition. Some glyco-proteins serve as identification tags that are specifically recognized by other cells.

Intercellular joining. Membrane proteins of adjacent cellsmay hook together in various kinds of junctions, such asgap junctions or tight junctions

Attachment to the cytoskeleton and extracellular matrix(ECM). Microfilaments or other elements of thecytoskeleton may be bonded to membrane proteins, a function that helps maintain cell shape and stabilizes the location of certain membrane proteins. Proteins that adhere to the ECM can coordinate extracellular and intracellular changes

4.

5.

6.

Glyco-protein

6 Major Functions Of Membrane Proteins6 Major Functions Of Membrane Proteins

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Outside

Plasmamembrane

InsideTransporter Cell surface

receptorEnzyme

Cell surface identitymarker

Attachment to thecytoskeletonCell adhesion

Functions of Plasma Membrane Proteins

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Cell JunctionsCell Junctions

Long-lasting or permanent Long-lasting or permanent connections between adjacent connections between adjacent cells, 3 types of cell junctions:cells, 3 types of cell junctions:

Tight junctionTight junction Anchoring junctionAnchoring junction Communicating junctionCommunicating junction

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Tight JunctionsTight Junctions Connect cells into sheets. Because these junctions form Connect cells into sheets. Because these junctions form

a tight seal between cells, in order to cross the sheet, a tight seal between cells, in order to cross the sheet, substances must pass through the cells, they cannot substances must pass through the cells, they cannot pass between the cells.pass between the cells.

Tightjunction

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Anchoring JunctionsAnchoring Junctions Attach the cytoskeleton of a cell to the matrix Attach the cytoskeleton of a cell to the matrix

surrounding the cell, or to the cytoskeleton of an surrounding the cell, or to the cytoskeleton of an adjacent cell.adjacent cell.

Cell1

Inter-cellularspace

Extracellular matrix

Intracellular attachment

proteins

Plasmamembranes

Transmembranelinking proteins

Cell2

Cytoskeletalfilament

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Communicating (Gap) JunctionsCommunicating (Gap) Junctions Link the cytoplasms of 2 cells together, Link the cytoplasms of 2 cells together,

permitting the controlled passage of small permitting the controlled passage of small molecules or ions between them. molecules or ions between them.

Two adjacent connexonsform a gap junction

Adjacent plasmamembranes

Connexon

Intercellular space

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Membrane CarbohydratesMembrane Carbohydrates

Membrane carbohydrates interact with the surface Membrane carbohydrates interact with the surface molecules of other cells, facilitating cell-cell molecules of other cells, facilitating cell-cell recognitionrecognition

Cell-cell recognition is a cell’s ability to distinguish Cell-cell recognition is a cell’s ability to distinguish one type of neighboring cell from anotherone type of neighboring cell from another

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Membrane TransportMembrane Transport The plasma membrane is the boundary that The plasma membrane is the boundary that

separates the living cell from its nonliving separates the living cell from its nonliving surroundingssurroundings

In order to survive, A cell must exchange In order to survive, A cell must exchange materials with its surroundings, a process materials with its surroundings, a process controlled by the plasma membranecontrolled by the plasma membrane

Materials must enter and leave the cell through Materials must enter and leave the cell through the plasma membrane.the plasma membrane.

Membrane structure results in selective Membrane structure results in selective permeability, it allows some substances to cross permeability, it allows some substances to cross it more easily than othersit more easily than others

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Passive transport is diffusion of a Passive transport is diffusion of a substance across a membrane with substance across a membrane with no energy investmentno energy investment

4 types4 types Simple diffusionSimple diffusion DialysisDialysis OsmosisOsmosis Facilitated diffusionFacilitated diffusion

Passive TransportPassive Transport

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DiffusionDiffusion The The net movementnet movement of a substance from an of a substance from an

area of higher concentration to an area of area of higher concentration to an area of lower concentration - down a lower concentration - down a concentration gradientconcentration gradient

Caused by the constant random motion of Caused by the constant random motion of all atoms and moleculesall atoms and molecules

Movement of individual atoms & Movement of individual atoms & molecules is random, but each substance molecules is random, but each substance moves down its own concentration moves down its own concentration gradient.gradient.

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Solutions and TransportSolutions and Transport

Slide 3.21Slide 3.21

Solution – homogeneous mixture of two or more components Solvent – dissolving medium

Solutes – components in smaller quantities within a solution

Intracellular fluid – nucleoplasm and cytosol

Extracellular fluid Interstitial fluid – fluid on the exterior of the cell within

tissues

Plasma – fluid component of blood

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Lumpof sugar

Diffusion

No net movement at equilibrium

Random movement leads to net movement down a concentration gradient

Water

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Diffusion Across a MembraneDiffusion Across a Membrane The membrane has pores large enough for the molecules to pass

through. Random movement of the molecules will cause some to pass

through the pores; this will happen more often on the side with more molecules. The dye diffuses from where it is more concentrated to where it is less concentrated

This leads to a dynamic equilibrium: The solute molecules continue to cross the membrane, but at equal rates in both directions.

Net diffusion Net diffusion Equilibrium

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Diffusion Across a MembraneDiffusion Across a Membrane Two different solutes are separated by a membrane that

is permeable to both Each solute diffuses down its own concentration gradient. There will be a net diffusion of the purple molecules

toward the left, even though the total solute concentration was initially greater on the left side

Net diffusion

Net diffusion

Net diffusion

Net diffusion Equilibrium

Equilibrium

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The Permeability of the Lipid BilayerThe Permeability of the Lipid Bilayer

Permeability FactorsPermeability Factors Lipid solubilityLipid solubility SizeSize ChargeCharge Presence of channels and transportersPresence of channels and transporters

Hydrophobic molecules are lipid soluble and can Hydrophobic molecules are lipid soluble and can pass through the membrane rapidlypass through the membrane rapidly

Polar molecules do not cross the membrane Polar molecules do not cross the membrane rapidlyrapidly

Transport proteins allow passage of hydrophilic Transport proteins allow passage of hydrophilic substances across the membranesubstances across the membrane

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Passive Transport ProcessesPassive Transport Processes• 3 special types of diffusion

that involve movement of materials across a semipermeable membrane

• Dialysis/selective diffusion of solutes

• Lipid-soluble materials

• Small molecules that can pass through membrane pores unassisted

• Facilitated diffusion - substances require a protein carrier for passive transport

• Osmosis – simple diffusion of water

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Diffusion of the Diffusion of the solventsolvent across a across a semipermeable membrane.semipermeable membrane.

In living systems the solvent is In living systems the solvent is always always waterwater, so biologists generally define , so biologists generally define osmosis as the diffusion of water osmosis as the diffusion of water across a semipermeable membrane:across a semipermeable membrane:

OsmosisOsmosis

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Lowerconcentrationof solute (sugar)

Higherconcentrationof sugar

Same concentrationof sugar

Selectivelypermeable mem-brane: sugar mole-cules cannot passthrough pores, butwater molecules can

More free watermolecules (higher

concentration)

Water moleculescluster around sugar molecules

Fewer free watermolecules (lowerconcentration)

Water moves from an area of higher free water concentration to an area of lower free water concentration

Osmosis

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Osmotic PressureOsmotic Pressure

Osmotic pressureOsmotic pressure of a solution is the of a solution is the pressure needed to keep it in pressure needed to keep it in equilibrium with pure Hequilibrium with pure H220.0.

The higher the [solutes] in a solution, The higher the [solutes] in a solution, the higher its osmotic pressure.the higher its osmotic pressure.

Tonicity is the ability of a solution to Tonicity is the ability of a solution to cause a cell to gain or lose water – cause a cell to gain or lose water – based on the concentration of solutesbased on the concentration of solutes

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My definition of OsmosisMy definition of Osmosis

Osmosis is the diffusion of water Osmosis is the diffusion of water across a semi-permeable membrane across a semi-permeable membrane from a hypotonic solution to a from a hypotonic solution to a hypertonic solutionhypertonic solution

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TonicityTonicity If 2 solutions have equal [solutes], they are called If 2 solutions have equal [solutes], they are called isotonicisotonic If one has a higher [solute], and lower [solvent], is If one has a higher [solute], and lower [solvent], is hypertonichypertonic The one with a lower [solute], and higher [solvent], is The one with a lower [solute], and higher [solvent], is hypotonichypotonic

Hypotonic solution Isotonic solution Hypertonic solution

H2O H2O H2O H2O

Lysed Normal Shriveled

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Facilitated Diffusion Facilitated Diffusion Diffusion of solutes through a semipermeable membrane with the help Diffusion of solutes through a semipermeable membrane with the help

of special transport proteins i.e. large polar molecules and ions that of special transport proteins i.e. large polar molecules and ions that cannot pass through phospholipid bilayer.cannot pass through phospholipid bilayer.

Two types of transport proteins can help ions and large polar Two types of transport proteins can help ions and large polar molecules diffuse through cell membranes:molecules diffuse through cell membranes: Channel proteins – provide a narrow channel for the substance to pass Channel proteins – provide a narrow channel for the substance to pass

through.through. Carrier proteins – physically bind to the substance on one side of Carrier proteins – physically bind to the substance on one side of

membrane and release it on the other.membrane and release it on the other.

EXTRACELLULARFLUID

Channel protein Solute

CYTOPLASMCarrier protein

Solute

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Facilitated DiffusionFacilitated Diffusion SpecificSpecific – each channel or carrier – each channel or carrier

transports certain ions or molecules onlytransports certain ions or molecules only PassivePassive – direction of net movement is – direction of net movement is

always down the concentration gradientalways down the concentration gradient SaturatesSaturates – once all transport proteins – once all transport proteins

are in use, rate of diffusion cannot be are in use, rate of diffusion cannot be increased furtherincreased further

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Active TransportActive Transport Uses energy (from ATP) to move a substance Uses energy (from ATP) to move a substance

against its natural tendency e.g. up a against its natural tendency e.g. up a concentration gradient.concentration gradient.

Requires the use of carrier proteins (transport Requires the use of carrier proteins (transport proteins that physically bind to the substance proteins that physically bind to the substance being transported).being transported).

2 types: 2 types: Membrane pumpMembrane pump (protein-mediated active (protein-mediated active

transport)transport) Coupled transportCoupled transport (cotransport). (cotransport).

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Membrane PumpMembrane Pump - A carrier protein uses energy from ATP to move a - A carrier protein uses energy from ATP to move a

substance across a membrane, up its concentration substance across a membrane, up its concentration gradient:gradient:

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One type of active transport systemOne type of active transport system

The Sodium-potassium PumpThe Sodium-potassium Pump

2. Na+ binding stimulatesphosphorylation by ATP.

1. Cytoplasmic Na+ binds to the sodium-potassium pump.

6. K+ is released and Na+

sites are receptive again; the cycle repeats.

3. Phosphorylation causes the protein to change its conformation, expelling Na+ to the outside.

4. Extracellular K+ binds to the protein, triggering release of the Phosphate group.

5. Loss of the phosphaterestores the protein’s original conformation.

P

EXTRACELLULARFLUID

Na+

CYTOPLASM

[Na+] low[K+] high

Na+

Na+

Na+

Na+

Na+

P ATP

Na+

Na+

Na+

P

ADP

K+

K+

K+

K+ K+

K+

[Na+] high[K+] low

P i

P i

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Coupled transportCoupled transport2 stages:2 stages:

1.1. Carrier proteinCarrier protein uses ATP to move a substance across the membrane uses ATP to move a substance across the membrane against its concentration gradient. Storing energy.against its concentration gradient. Storing energy.

2.2. Coupled transportCoupled transport protein allows the substance to move down its protein allows the substance to move down its concentration gradient using the stored energy to move a second concentration gradient using the stored energy to move a second substance up its concentration gradient:substance up its concentration gradient:

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Bulk TransportBulk Transport Allows small particles, or groups of Allows small particles, or groups of

molecules to enter or leave a cell molecules to enter or leave a cell without actually passing through the without actually passing through the membrane.membrane.

2 mechanisms of bulk transport: 2 mechanisms of bulk transport: endocytosis and exocytosis.endocytosis and exocytosis.

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EndocytosisEndocytosis

The plasma membrane envelops small The plasma membrane envelops small particles or fluid, then seals on itself to form particles or fluid, then seals on itself to form a vesicle or vacuole which enters the cell:a vesicle or vacuole which enters the cell: PhagocytosisPhagocytosis PinocytosisPinocytosis

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Phagocytosis

The substance engulfed is a solid particleThe substance engulfed is a solid particle

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Process of PhagocytosisProcess of Phagocytosis

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Pinocytosis

TheThe substance engulfed is a liquidsubstance engulfed is a liquid

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Exocytosis Exocytosis The reverse of endocytosisThe reverse of endocytosis During this process, the membrane of a vesicle fuses During this process, the membrane of a vesicle fuses

with the plasma membrane and its contents are released with the plasma membrane and its contents are released outside the cell:outside the cell:

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Cells CommunicationCells Communication

• Direct contact• Paracrine signaling• Endocrine signaling• Synaptic signaling

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Direct ContactDirect Contact• Cells touch each other and signal molecules travel

through special connections called communicating junctions

• Communicating Junctions link the cytoplasms of 2 cells together, permitting the controlled passage of small molecules or ions between them.

Adjacent connexonsform a gap junction

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(a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid.

(b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.

Hormone travelsin bloodstreamto target cells

(c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells.

Local regulator diffuses through extracellular fluid

Secretingcell

Target cell

Secretoryvesicle

Electrical signalalong nerve celltriggers release ofneurotransmitter

Neurotransmitter diffuses across

synapse

Target cellis stimulated

Local signaling Long-distance signaling

Endocrine cellBloodvessel

Targetcell

Local and long-distance cell Local and long-distance cell communication in animalscommunication in animals

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Cell SignalingCell Signaling

EXTRACELLULARFLUID

Receptor

Signal molecule

Relay molecules in a signal transduction pathway

Plasma membraneCYTOPLASM

Activationof cellularresponse

Reception Transduction Response1 2 3

• The cells of a organism communicate with each other by releasing signal molecules that bind to receptor proteins located either on or inside of target cells.

• Three stages of cell signaling:• Reception - each target cell has receptors that detect a specific signal molecule and binds to

it

• Transduction – binding of the signal molecule changes the receptor protein in some way that initiates transduction or conversion of the signal to a form that can bring about a specific cellular response

• Response – transduced signal triggers a specific cellular response, any cell activity

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ReceptionReception• A signal molecule binds to a receptor protein,

causing it to change shape• The binding between signal molecule (ligand)

and receptor is highly specific• A conformational change in a receptor

• Is often the initial transduction of the signal

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ReceptorsReceptors• Intracellular receptors

• Some signal molecules that are small or hydrophobic can pass through the plasma membrane and bind to receptors located inside the cell

• Intracellular receptors are cytoplasmic or nuclear proteins

• Cell surface receptors. - Signal molecules that cannot pass through the plasma membrane bind to receptors located on the surface of the membrane

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Intracellular Receptors Intracellular Receptors

• Gene Regulators• Signal molecule joins to the receptor, the receptor

changes shape and a DNA binding site is exposed.• The DNA binding site joins to a specific segment of

DNA and activates (or suppresses) a particular gene

• Enzyme Receptor• These receptors function as enzymes – proteins that

catalyze (speed up) specific chemical reactions. • When a signal molecule joins to the receptor, the

receptor’s catalytic domain is activated (or deactivated).

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Hormone(testosterone)

EXTRACELLULARFLUID

Receptorprotein

Plasmamembrane

Hormone-receptorcomplex

DNA

mRNA

NUCLEUS

CYTOPLASM

New protein

The steroid hormone testosterone passes through the plasma membrane.

1

Testosterone bindsto a receptor proteinin the cytoplasm,activating it.

2

The hormone-receptor complexenters the nucleusand binds to specific genes.

3

The bound proteinstimulates thetranscription ofthe gene into mRNA.

4

The mRNA istranslated into aspecific protein.

5

  Steroid hormone interacting with an intracellular receptorSteroid hormone interacting with an intracellular receptor

51Figure 6-5

Signal Pathways: Membrane Receptors Signal Pathways: Membrane Receptors

• Receptors located on the surface of the membrane• Chemical or ligand-gated ion

channels• Enzymatic receptors• G-protein-linked receptors

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Chemically Gated Ion ChannelsChemically Gated Ion Channels

• Open or close when the signal molecule binds to the channel.

Gate close

Cellularresponse

Gate open

Gate close

Ligand-gatedion channel receptor

Plasma Membrane

Signalmolecule(ligand)

GateClosed Ions

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Enzymatic ReceptorsEnzymatic Receptors• Embedded in the plasma membrane, with their catalytic site exposed inside

the cell. • Catalytic site activated when the signal molecule joins to the receptor. • Function as protein kinases (enzymes that phosphorylate proteins.)

Signalmolecule

Signal-binding site

CYTOPLASM

Tyrosines

Signal molecule Helix in the

Membrane

Tyr

TyrTyr

TyrTyr

TyrTyr

TyrTyr

TyrTyr

Tyr

Tyr

TyrTyr

TyrTyr

Tyr Tyr

TyrTyr

TyrTyr

Tyr

Tyr

TyrTyr

TyrTyr

Tyr

DimerReceptor tyrosinekinase proteins(inactive monomers)

PPP

P

P

P Tyr

TyrTyr

TyrTyr

TyrP

PP

PP

PCellularresponse 1

Inactiverelay proteins

Activatedrelay proteins

Cellularresponse 2

Activated tyrosine-kinase regions(unphosphorylateddimer)

Fully activated receptortyrosine-kinase(phosphorylateddimer)

6 ATP 6 ADP

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Signal-binding site

G-protein-linkedreceptor

Plasma Membrane

EnzymeG-protein(inactive)CYTOPLASM

Cellular response

Activatedenzyme

Activatedreceptor

Signal molecule Inactiveenzyme

Segment thatinteracts withG proteins

GDP

GDP

GTP

GTP

P i

GDP

G-protein-linked Receptors

• Signal molecule joins to a receptor, the receptor activates a G protein

• The activated G protein can then activate an ion channel or enzyme in the plasma membrane.

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Second MessengersSecond Messengers• Some enzymatic

receptors and most G-protein-linked receptors relay their message into the cell by activating other molecules or ions inside the cell.

• These molecules and ions, called second messengers, transmit the message within the cell.

• The 2 most common second messengers are cAMP and Ca++

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cAMP Second MessengercAMP Second MessengerG-protein-signaling pathwayG-protein-signaling pathway

1. Signal molecule binds to surface receptor

2. Surface receptor activates a G protein

3. G protein activates the membrane-bound enzyme, adenylyl cyclase

4. Adenylyl cyclase catalyzes synthesis of camp, which binds to a target protein

5. Target protein initiates cellular change

First messenger(signal moleculesuch as epinephrine)

ATP

GTP

cAMP

Proteinkinase A

Cellular responses

G-protein-linkedreceptor

Adenylylcyclase

G protein

Second messenger

57

Cyclic AMPCyclic AMP

O–O O

O

N

O

O

O

O

P P P

P

P P

O

O

O

O

O

OH

CH2

NH2 NH2 NH2

N

N

N

N

N

N

N

N

N

N

NO

O

O

ATP

Ch2CH2

O

OH OH

P

O O

H2O

HOAdenylyl cyclase Phoshodiesterase

Pyrophosphate

Cyclic AMP AMPOH OH

O

i

58

Cyclic AMP PathwayCyclic AMP Pathway

59

Calcium and IPCalcium and IP33 in signaling pathways in signaling pathways1. Signal molecule binds

to surface receptor

2. Surface receptor activates a G protein

3. G protein activates the membrane-bound enzyme, phospholipase C

4. Phospholipase C catalyzes synthesis of inositol triphosphate (IP3), which stimulates release of Ca++ from ER

5. Released Ca++ initiates cellular change

2 3

IP3 quickly diffuses throughthe cytosol and binds to an IP3–gated calcium channel in the ERmembrane, causing it to open.

4 The calcium ionsactivate the nextprotein in one or moresignaling pathways.

6 Calcium ions flow out ofthe ER (down their con-centration gradient), raisingthe Ca2+ level in the cytosol.

5

DAG functions asa second messengerin other pathways.

Phospholipase C cleaves aplasma membrane phospholipidcalled PIP2 into DAG and IP3.

EXTRA-CELLULARFLUID

Signal molecule(first messenger)

G protein

G-protein-linkedreceptor

Variousproteinsactivated

Endoplasmicreticulum (ER)

Phospholipase CPIP2

IP3

(second messenger)

DAG

Cellularresponses

GTP

Ca2+

(second messenger)

Ca2+

IP3-gatedcalcium channel

A signal molecule bindsto a receptor, leading toactivation of phospholipase C.

1

CYTOSOL

60Figure 6-9

Signal Pathway: Signal TransductionSignal Pathway: Signal Transduction

Steps of a cascade

Steps of signal transduction pathway form a cascade

61

  A Phosphorylation CascadeA Phosphorylation CascadeSignal molecule

Activeproteinkinase

1

Activeproteinkinase

2

Activeproteinkinase

3

Inactiveprotein kinase

1

Inactiveprotein kinase

2

Inactiveprotein kinase

3

Inactiveprotein

Activeprotein

Cellularresponse

Receptor

P

P

P 

P

P

P

ATP

ADP

ADP

ADP

ATP

ATP

PP

PP

PP

Activated relaymolecule

A relay moleculeactivates protein kinase 1.1

Active protein kinase 1transfers a phosphate from ATPto an inactive molecule ofprotein kinase 2, thus activatingthis second kinase.

2

Active protein kinase 2then catalyzes the phos-phorylation (and activation) ofprotein kinase 3.

3

Finally, active proteinkinase 3 phosphorylates aprotein (pink) that brings about the cell’s response tothe signal.

4

Enzymes called proteinphosphatases (PP)catalyze the removal ofthe phosphate groupsfrom the proteins, making them inactiveand available for reuse.

5

i

i

i

Phosphorylation cascade

62Figure 6-7

Signal Pathways: Signal AmplificationSignal Pathways: Signal Amplification• Transducers convert extracellular signals into

intracellular messages which create a response

63

Signal AmplificationSignal Amplification

Glucose-1-phosphate(108 molecules)

Glycogen

Active glycogen phosphorylase (106)Inactive glycogen phosphorylase

Active phosphorylase kinase (105)Inactive phosphorylase kinase

Inactive protein kinase AActive protein kinase A (104)

ATPCyclic AMP (104)

Active adenylyl cyclase (102)

Inactive adenylyl cyclase

Inactive G protein

Active G protein (102 molecules)

Binding of epinephrine to G-protein-linked receptor (1 molecule)

Transduction

Response

Reception

• Stimulation of glycogen breakdown in a liver cell by epinephrine