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Professor of Cellular & Molecular Physiology and Cell Biology |
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| Caplan lab website Phone: (203) 785-7316 Lab: (203) 785-6833 Fax: (203) 785-4951 e-mail: michael.caplan@yale.edu |
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Department of Cellular & Molecular Physiology <Courier Address> |
Our studies of these "sorting signals" make use of families of transport proteins, each of whose members are sorted to different surfaces despite extensive homology. This approach has allowed us to identify segments of these molecules that contribute to their sorting behaviors as well as to their physiologic properties. Quite recently we have found that a novel class of membrane proteins, known as the tetraspanins, may play critical roles in the sorting and trafficking of a wide variety of epithelial transport proteins.
Cystic fibrosis is a human disease that is attributable to the mis-trafficking of an ion transport protein. Cystic fibrosis is caused by mutations in the gene encoding a chloride channel, the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The most common disease causing mutation results in the production of a protein that is mis-folded and can not get to the apical surfaces of secretory epithelial cells. Instead, it is trapped in the endoplasmic reticulum and rapidly degraded. We have identified a new class of compounds that appear to release the trapped mutant form of CFTR and allow it to function appropriately at the cell surface. One of the compounds that we are studying appears to be non-toxic and is able to correct a measurable defect in a mouse model of cystic fibrosis.
Polycystic kidney disease is also caused by mutations in genes encoding membrane proteins, polycystin-1 and 2. We have identified novel mechanisms that regulate the distributions of these polycystin proteins and that explain their capacity to participate in signaling pathways that communicate between the cell surface and the nucleus.
for PDFCourtois-Coutry N, Roush DL, Rajendran V, McCarthy JB, Geibel J, Kashgarian M, Caplan MJ. (1997) A
Tyrosine-Based Signal Targets H/K-ATPase to a Regulated Compartment and is Required for the Cessation of Gastric
Acid Secretion. Cell 90: 501-510.
Muth TR, Ahn J, Caplan MJ. (1998) Identification of Sorting Determinants in the C-Terminal Cytoplasmic Tails
of the 
-Aminobutyric Acid Transporters GAT-2 and GAT-3*. J Biol Chem. 273: 25616-25627.
Dunbar LA, Aronson PL, Caplan MJ. (2000) A Transmembrane Segment Determines the Steady-State Localization of
an Ion Transporting Adenosine Triphosphatase. J Cell Biol. 148: 769-778.
McCarthy JB, Lim ST, Elkind NB, Trimmer JS, Duvoisin RM, Rodriguez-Boulan E, Caplan MJ. (2001) The
C-terminal tail of the metabotropic glutamate receptor (mGluR7) is necessary but not sufficient for cell surface
delivery and polarized targeting in neurons and epithelia. J Biol Chem. 276: 9133-9140.
Muth TR & Caplan MJ. (2003) Transport Protein Trafficking in Polarized Cells. Ann Rev Cell Dev Biol. 19: 333-366.
Grimm DH, Cai Y, Chauvet V, Rajendran V, Zeltner R, Geng L, Avner ED, Sweeney W, Somlo S, and Caplan MJ. (2003) Polycystin-1 distribution is modulated by polycystin-2 expression in mammalian cells. J Biol Chem., 278: 36786-36793.
Duffield A, Kamsteeg EJ, Brown AN, Pagel P, Caplan MJ. (2003) The tetraspsanin CD63 enhances the internalization of the H,K-ATPase ß-subunit. Proc Nat Acad. Sci. USA 100: 15560-15565.
Egan ME, Pearson M, Weiner SA, Rajendran V, Rubin D, Gloeckner-Pagel J, Canny S, Du K, Lukacs G, Caplan MJ. (2004) Curcumin, a major constitutent of turmeric, corrects cystic fibrosis defects. Science 304: 600-602.
Duffield A, Fölsch H, Mellman I, Caplan MJ. (2004) Sorting of H,K-ATPase ß-subunit in MDCK and LLC-PK1 cells is independent of µ1B adaptin expression. Traffic. 5(6): 449-61.
