TRPV2 activation reorganizes actin cytoskeleton, induces neurite initiation and branching by altering cAMP levels

Understanding of molecules and their role in neurite initiation and/or extension is not only helpful to prevent different neurodegenerative diseases but also can be important by which neuronal damages can be repaired. In this work we explored the role of TRPV2, a non-selective cation channel in the context of neurite functions. Using western blot, immunofluorescence, and live cell Ca2+-imaging; we confirm that functional TRPV2 is endogenously present in the F11 cell, a model system mimicking peripheral neuron. In F11 cells TRPV2 localizes in specific sub-cellular regions enriched with filamentous actin, such as in growth cone, filopodia, lamellipodia and in neurites. TRPV2 regulates actin cytoskeleton and also interacts with soluble actin. Ectopic expression of TRPV2-GFP but not GFP-only in F11 cell induces more primary and secondary neurites, confirming its role in neurite initiation, extension and branching events. TRPV2-mediated neuritogenesis is dependent on wild-type TRPV2 as cells expressing TRPV2 mutants reveal no neuritogenesis. However, TRPV2-mediated neuritogenesis is unperturbed by the chelation of intracellular Ca2+ by BAPTA-AM, and thus involves Ca2+-independent signaling events also. We demonstrate that pharmacological modulation of TRPV2 alters cellular cAMP levels. These findings are relevant to understand the sprouting of new neurites, neuroregeneration and neuronal plasticity at the cellular, subcellular and molecular level. Such understanding may have border implication in neurodegeneration and peripheral neuropathy.