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Biochemical, functional, and genetic studies support a model in which PKD1 physically interacts with TRPP2 to form an ion channel complex that conveys extracellular stimuli to ionic currents. However, the molecular identity of these extracellular stimuli remains elusive. Functional studies in cell culture show that TRPP2 can be activated in response to mechanical cues (fluid shear stress) and\/or receptor tyrosine kinase (RTK) and G protein-coupled receptor (GPCR) activation at the cell surface. Recent genetic studies in Chlamydomonas reinhardtii show that CrPKD2 functions in a pathway linking cell-cell adhesion and Ca<jats:sup>2+<\/jats:sup>signaling. The mode of activation depends on protein-protein interactions with other channel subunits and auxiliary proteins. Therefore, understanding the mechanisms underlying the molecular makeup of TRPP2-containing complexes is critical in delineating the mechanisms of TRPP2 activation and, most importantly, the mechanisms by which naturally occurring mutations in pkd1 or pkd2 lead not only to ADPKD, but also to other defects reported in model organisms lacking functional TRPP2. This review focuses on the molecular assembly, function, and regulation of TRPP2 as a cell surface cation channel and discusses its potential role in Ca<jats:sup>2+<\/jats:sup>signaling and ADPKD pathophysiology.<\/jats:p>","DOI":"10.1152\/ajprenal.90277.2008","type":"journal-article","created":{"date-parts":[[2009,2,26]],"date-time":"2009-02-26T02:27:58Z","timestamp":1235615278000},"page":"F1-F9","source":"Crossref","is-referenced-by-count":62,"title":["Function and regulation of TRPP2 at the plasma membrane"],"prefix":"10.1152","volume":"297","author":[{"given":"Leonidas","family":"Tsiokas","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.08.043"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M504359200"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1038\/embor.2008.29"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2008.70"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.67.3.606"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1038\/312315a0"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.97.2.397"},{"key":"R8","doi-asserted-by":"crossref","unstructured":"Breyer JA, Cohen S.The epidermal growth factor precursor isolated from murine kidney membranes. 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