Post on 16-Dec-2015
Aquaporins
What are Aquaporins?
How many organisms have them?
Why are they important?
Who discovered them?
Aquaporins
There are at least 12 Aquaporin proteins present in the human body.
Mutations in some lead to disease.
Some are essential for numerous body functions.
Without them, we would die of dehydration.
What do they look like?
Constructed of 6 alpha-helices in a right hand configuration
Form tetramers, each acts as a monomer.
http://upload.wikimedia.org/wikipedia/commons/a/a5/Aquaporin-Sideview.png
Types of Aquaporin
Aquaporins vs Aquaglyceroporins
What is the difference?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658677/figure/fig4/
How do they work?
NPA motif
Ar/R selective filter
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2658677/figure/fig3/
What is my project?
Comparing the Aquaporin and Aquaporin like genes in the human genome.
20 sequences found
16 used for phylogeny tree once reduced
Purpose of the Project?
To possibly find the gene that gave rise to the numerous Aquaporin like genes found today.
A better understanding of Aquaporin genes could lead to effective treatments for diseases related to their mutations.
Understanding the similarities and differences in Aquaporins provides a better understanding of cellular function and specialization.
Results
Results with no outgroup (n=16)
Results with Danio rerio as an outgroup (n=17)
Results with other outgroups?
Resources
Agre P, Preston GM, Smith BL, Jung JS, Raina S, Moon C, Guggino WB, Nielsen S (1 October 1993). "Aquaporin CHIP: the archetypal molecular water channel". Am. J. Physiol. 265 (4 Pt 2): F463–76.
Agre P (2006). "The aquaporin water channels". Proc Am Thorac Soc 3 (1): 5–13.
Damiano,A., Zotta,E., Goldstein,J., Reisin,I. and Ibarra,C. (2001) “Water channel proteins AQP3 and AQP9 are present in syncytiotrophoblast of human term placenta”. Placenta 22 (8-9), 776-781.
Dibas AI, Mia AJ, Yorio T (1998). "Aquaporins (water channels): role in vasopressin-activated water transport". Proc. Soc. Exp. Biol. Med. 219 (3): 183–99.
Fischer,H., Stenling,R., Rubio,C. and Lindblom,A. (2001) “Differential expression of aquaporin 8 in human colonic epithelial cells and colorectal tumors”. BMC Physiol. 1, 1.
Fu D, Lu M (2007). "The structural basis of water permeation and proton exclusion in aquaporins". Mol. Membr. Biol. 24 (5-6): 366–74.
Gonen T, Walz T (2006). "The structure of aquaporins". Q. Rev. Biophys. 39 (4): 361–96.
Resources (cont.)
de Groot BL, Grubmüller H (2001). "Water permeation across biological membranes: mechanism and dynamics of aquaporin-1 and GlpF". Science 294 (5550): 2353–2357.
Hatakeyama,S., Yoshida,Y., Tani,T., Koyama,Y., Nihei,K., Ohshiro,K., Kamiie,J.I., Yaoita,E., Suda,T., Hatakeyama,K. and Yamamoto,T. (2001) “Cloning of a new aquaporin (AQP10) abundantly expressed in duodenum and jejunum”. Biochem. Biophys. Res. Commun. 287 (4), 814-819.
Ishibashi,K., Kuwahara,M., Gu,Y., Tanaka,Y., Marumo,F. and Sasaki,S. (1998) “Cloning and functional expression of a new aquaporin (AQP9) abundantly expressed in the peripheral leukocytes permeable to water and urea, but not to glycerol”. Biochem. Biophys. Res. Commun. 244 (1), 268-274.
Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (August 2005). "IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel". J. Exp. Med. 202 (4): 473–7.
Mobasheri, A., Shakibaei, M., Marples, D. (2004) “Immunohistochemical localization of aquaporin 10 in the apical membranes of the human ileum: a potential pathway for luminal water and small solute absorption”. Histochem. Cell Biol. Jun;121(6):463-71.
Preston GM, Carroll TP, Guggino WB, Agre P. Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein. Science 1992;256:385–387.
Reizer J, Reizer A, Saier Jr MH (1993). "The MIP family of integral membrane channel proteins: sequence comparisons, evolutionary relationships, reconstructed pathway of evolution, and proposed functional differentiation of the two repeated halves of the proteins". Crit. Rev. Biochem. Mol. Biol. 28 (3): 235–257.
Resources (cont.)
Savelkoul,P.J., De Mattia,F., Li,Y., Kamsteeg,E.J., Konings,I.B., van der Sluijs,P. and Deen,P.M. (2009) “p.R254Q mutation in the aquaporin-2 water channel causing dominant nephrogenic diabetes insipidus is due to a lack of arginine vasopressin-induced phosphorylation” Hum. Mutat. 30 (10), E891-E903.
Tajkhorshid E, Nollert P, Jensen MØ, Miercke LJ, O'Connell J, Stroud RM, Schulten K (2002). "Control of the selectivity of the aquaporin water channel family by global orientational tuning". Science 296 (5567): 525–30.
Unknown author. (2003) “The Nobel Prize in Chemistry 2003”. Nobel Foundation. http://nobelprize.org/nobel_prizes/chemistry/laureates/2003/public.html Retrieved 4/14/2010.
Walter F., PhD. Boron (2005). Medical Physiology: A Cellular And Molecular Approaoch. Elsevier/Saunders. Page 842.
Wistow GJ, Pisano MM, Chepelinsky AB (1991). “Tandem sequence repeats in transmembrane channel proteins.” Trends Biochem. Sci. 16 170-1.
Entrez Gene Link MIP http://www.ncbi.nlm.nih.gov/gene/4284
Entrez Gene Link AQP5 http://www.ncbi.nlm.nih.gov/gene/362
Entrez Gene Link AQP6 http://www.ncbi.nlm.nih.gov/gene/363
Entrez Gene Link AQP7 http://www.ncbi.nlm.nih.gov/gene/364
Entrez Gene Link AQP8 http://www.ncbi.nlm.nih.gov/gene/343
Software Used
FigTree Version 1.3.1 http://tree.bio.ed.ac.uk/software/figtree/
MAFFT Version 6.717 http://mafft.cbrc.jp/alignment/software/macosx.html
RAxML Version 7.0.4 http://icwww.epfl.ch/~stamatak/index-Dateien/Page443.htm
Seaview Version 4.1.2 http://pbil.univ-lyon1.fr/software/seaview.html