My lab moved to the NIH July 17, 2010 and the funds were used to setup the lab. Major equipment purchased are patch-clamop setups-2, imaging setups-2, confocal microscop-1, TIRF microscop-1. So far we received only a fraction of our other orders and when we will manage to setup the lab, actual work will start. While waiting for orders to arrive, in collaboration with Dr. Ambudkar we completed a study reporting the unique expression and function of Orai1, TRPC channels and STIM1 in secretory cells. We discovered that acinar cells express to type of Ca2+ influx channels, STIM1-Orai1-TRPC1 complex and a separate STIM1-TRPC1 complex in separate plasma membrane domains. The channels appear to have separate but complimentary function in mediating cellular activity. A manuscript summarizing these studies was submitted to Traffic. We complete another study in which we discovered that TRPC channels can function in two modes, STIM1-dependent and STIM1-independent modes when stimulated by G proteins-coupled receptors. The results show that at physiological low agonist stimulation STIM1 gates TRPC channels by electrostatic interaction that is mediated by two conserved negative charges in the C terminus of TRPC channels and two positive charges in STIM1 polybasic, C terminus domain. However, at intense stimulation that mimic the pathological state of Ca2+ signaling this control is lost and the channels are activated in a STIM1-independent mode to constitutively activate Ca2+ influx. A manuscript summarizing these studies was submitted to The Journal of Biological Chemistry.
| Zeng, Mei; Szymczak, Mitchell; Ahuja, Malini et al. (2017) Restoration of CFTR Activity in Ducts Rescues Acinar Cell Function and Reduces Inflammation in Pancreatic and Salivary Glands of Mice. Gastroenterology 153:1148-1159 |
| Verkhratsky, Alexei; Muallem, Shmuel (2017) The forefront of technology of science: Methods for monitoring cell function. Cell Calcium 64:1-2 |
| Chung, Woo Young; Jha, Archana; Ahuja, Malini et al. (2017) Ca2+ influx at the ER/PM junctions. Cell Calcium 63:29-32 |
| Bretou, Marine; Sáez, Pablo J; Sanséau, Doriane et al. (2017) Lysosome signaling controls the migration of dendritic cells. Sci Immunol 2: |
| Ahuja, Malini; Schwartz, Daniella M; Tandon, Mayank et al. (2017) Orai1-Mediated Antimicrobial Secretion from Pancreatic Acini Shapes the Gut Microbiome and Regulates Gut Innate Immunity. Cell Metab 25:635-646 |
| Erkhembaatar, Munkhsoyol; Gu, Dong Ryun; Lee, Seoung Hoon et al. (2017) Lysosomal Ca(2+) Signaling is Essential for Osteoclastogenesis and Bone Remodeling. J Bone Miner Res 32:385-396 |
| Muallem, Shmuel; Chung, Woo Young; Jha, Archana et al. (2017) Lipids at membrane contact sites: cell signaling and ion transport. EMBO Rep 18:1893-1904 |
| Muallem, Shmuel; Jha, Archana (2017) Opening the Orai1 gates. Sci Signal 10: |
| Jha, Archana; Muallem, Shmuel (2016) The CAR that drives Ca2+ to Orai1. Sci Signal 9:fs5 |
| Hegyi, Péter; Wilschanski, Michael; Muallem, Shmuel et al. (2016) CFTR: A New Horizon in the Pathomechanism and Treatment of Pancreatitis. Rev Physiol Biochem Pharmacol 170:37-66 |
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