Abstract
Ca2+ is an important signaling mediator in neuronal guidance, outgrowth, and retraction. Amplitude, frequency and subcellular location of Ca2+ transients regulate development, function and survival of neurons. Transient receptor potential vanilloid 2 (TRPV2) is a nonselective Ca2+-permeable cation channel implicated in growth factor signaling and neuronal cell development. TRPV2 shows constitutive activity, suggesting that its subcellular location is important for its function; however, the molecular mechanisms by which TRPV2 trafficking is regulated are not well understood. We identified several TRPV2 binding partners from mouse brain implicated in neurite extension and nerve growth factor (NGF) signaling. In heterolgous expression systems, NGF signaling increased expression and changed the localization of TRPV2, while IGF-1 had little to no effect on TRPV2 localization. Studying endogenous TRPV2 has proven difficult since specific pharmacological modulators are unavailable and TRPV2 antibodies have not been extensively characterized and validated. Our laboratory has developed highly specific monoclonal TRPV2 antibodies by using full-length, tetrameric TRPV2 as an antigen. These antibodies have allowed us to identify endogenous expression, localization and the effects of growth factors on TRPV2 in neuronal cell lines and DRG neurons. These results will enhance our understanding of the key players in Ca2+ signaling during neuronal cell development.
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