Ca2+ signaling: Changes in cytoplasmic Ca2+ concentration serve to rapidly transmit information from the cell surface to the cell interior to regulate a variety of cellular functions. To control the messenger and effector roles of Ca2+, cells generate precisely defined Ca2+ signals, often in the form of propagating Ca2+ waves, by assembling Ca2+ signaling complexes in cellular microdomains. Compartmentalization of Ca2+ signaling is most prominent in polarized cells such as neurons and epithelial cells.
In our laboratory we study Ca2+ signaling in polarized cells and their role in cellular function from exocytosis to gene regulation. Electrophysiological, confocal and TIRF imaging techniques are used to monitor Ca2+ in subcellular compartments and follow the activity of Ca2+ pumps and channels. These approaches are complemented by a variety of molecular techniques to study organization of Ca2+ signaling complexes. Major questions currently pursued include the mechanism of signaling specificity among different Gq-coupled receptors, the mode of communication between Ca2+ transporters in the endoplasmic reticulum and those residing at the plasma membrane, the role of different Ca2+ pools in regulation of specific transcription factors.
HCO3- transport and Cystic Fibrosis: Another aspect of our work is regulation of fluid and electrolyte secretion by epithelial cells. A key protein regulating epithelial function is the Cystic Fibrosis Transmembrane Regulator (CFTR). Our work is geared towards understanding how CFTR regulates the activity of other transport proteins, in particular anion transporters that participate in epithelial HCO3- secretion. We found a new family of electrogenic Cl- and HCO3- transporters (the SLC26A family) that plays a major role in epithelial HCO3- secretion. We study the rciprocal regulation of the SLC26A transporters and CFTR and their relevance to epithelial transport and to CF and other Cl- and HCO3- transport related diseases.
RESEARCH INTERESTS
Ca2+ signaling and ion transport in secretory cells
CFTR, SLC26A transporters and Cystic Fibrosis
RECENT PUBLICATIONS
Shcheynikov N, Wang Y, Park M, Ko SB, Dorwart M, Naruse S, Thomas PJ, Muallem S, "Coupling modes and stoichiometry of Cl-/HCO3- exchange by slc26a3 and slc26a6." J Gen Physiol, 127(5):511-24, May 2006
Yuan JP, Zeng W, Huang GN, Worley PF, Muallem S, "STIM1 heteromultimerizes TRPC channels to determine their function as store-operated channels." Nat Cell Biology, 9(6):636-45, June 2007
Wang Y, Soyombo AA, Shcheynikov N, Zeng W, Dorwart M, Marino CR, Thomas PJ, Muallem S, "Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO(3)(-) secretion: relevance to cystic fibrosis." EMBO J, [Epub ahead of print] October 2006
Huang GN, Zeng W, Kim JY, Yuan JP, Han L, Muallem S, Worley PF, "STIM1 carboxyl-terminus activates native SOC, I(crac) and TRPC1 channels" Nat Cell Biol, 8(9)::1003-10., September 2006
Wang X, Zeng W, Kim MS, Allen PB, Greengard P, Muallem S, "Spinophilin/neurabin reciprocally regulate signaling intensity by G protein-coupled receptors." EMBO Journal, 6;26(11):2768-76., June 2007
SIGNIFICANT PUBLICATIONS
Kiselyov K, Xu X, Mozhayeva G, Kuo T, Pessah I, Mignery G, Zhu X, Birnbaumer L, Muallem S, "Functional interaction between InsP3 receptors and store-operated Htrp3 channels." Nature, 396(6710):478-82, December 1998
Kim HJ, Li Q, Tjon-Kon-Sang S, So I, Kiselyov K, Soyombo AA, Muallem S., "A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype" EMBO Journal, 27(8)::1197-1205, 2008
Park M, Li Q, Shcheynikov N, Zeng W, and Muallem S., "NaBC1 Is a Ubiquitous" Mol Cell, 16:331-41, March 2004
Choi JY, Muallem D, Kiselyov K, Lee MG, Thomas PJ, Muallem S, "Aberrant CFTR-dependent HCO3- transport in mutations associated with cystic fibrosis." Nature, 410(6824):94-7, March 2001
Ko SB, Shcheynikov N, Choi JY, Luo X, Ishibashi K, Thomas PJ, Kim JY, Kim KH, Lee MG, Naruse S, Muallem S, "A molecular mechanism for aberrant CFTR-dependent HCO(3)(-) transport in cystic fibrosis." EMBO J, 21(21):5662-72, November 2002
Kim HJ, Li Q, Tjon-Kon-Sang S, So I, Kiselyov K, Soyombo AA, Muallem S., "A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype" EMBO Journal, 27(8)::1197-1205, 2008
Point and right click (click and hold for Mac users) your mouse onand select "Save this link (or target) as..." option to save the file to your local computer.
and select "Save this link (or target) as..." option to save the file to your local computer.