Biochemical Mechanisms for Long-term Information Storage at the Cellular Level
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Transcript of Biochemical Mechanisms for Long-term Information Storage at the Cellular Level
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Biochemical Mechanisms for Long-term Information
Storage at the Cellular Level
From Mechanisms of Memory by J. David Sweatt, Ph.D.
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Protein Synthesis Dependence of L-LTP
Kang et al. (2001) Cell 106:771-783.
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CREB Binding Protein (CBP)
cAMP Response Element5’-TGACGTCA-3’
TATA Sequence
CREB CREB
Basal Transcription Factor IID (TFIID)
Complex
ser 133 ser 133
RNA Helicase A
RNAPolymerase II
Histone
pKAF
acetylation
TargetGene
PO4 PO4
The CREB/CRE Gene Regulation System
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Figure courtesy of Jennifer GatchelBrookhaven National Protein Structure Data Bank, Rendered with Rasmol
Crystal Structure of CREB bound to the CRE
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Activity-dependent Regulation of Gene Expression
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CRE SRE zif268
C/EBP krox20
AMPARHOMERBDNFNT-3
MKP-1SSAT
Arc
CBP/CREB
CaMKIV + ERK
Elk-1
RSK2
Transcriptional Regulation Pathways
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Steward and Worley (2001) PNAS 98:7062-7068.
Activity-dependent Arc Expression and Dendritic Localization
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Hypothetical Mechanisms for Activity-dependent changes in Synaptic Structure
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Presynaptic
Postsynaptic
IntegrinsIntegrins
Ca++Ca++
actin
Pax
illin
FAK (Focal Adhesion Kinase)
grb2/sos cas/crk src
ERK JNK
α αββrho rac
Dynamiccytoskeletalregulation
Cadherins
Catenins
?
DMPK
MyosinPhosphatase
CytoskeletalMyosin II
-
-
α-actinintalin
vincu
lin α-actinin
Signaling Mechanisms Used by Integrins and Cadherins
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Villarreal et al. (2002). Nat. Neurosci. 5:48-52.
L-LTP Decay is an Active Process
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Neurogenesis in the Adult CNS
Gould et al. (1999) Nat. Neurosci. 2:260-265.