Interaction between PSD 95 and TRPV4 through PDZ domain controls TRPV4's localization and activity.

The TRPV4 cation channel, is expressed in a broad range of tissues where it participates in generation of Ca2+ signal and/or depolarization of membrane potential. Here, we identified post synaptic density protein 95 (PSD95) as an interacting protein of this epithelial Ca2+ channel using confocal microscopy analysis and immunological assay. Using co-immunoprecipitation assays, we demonstrated that PSD95 was part of the TRPV4 protein complex. PSD95 protein was specifically associated with the C-terminal tail of TRPV4 to form a complex. A TRPV4 tail deletion mutant ({Delta}DAPL871: 4d) exhibited a diminished capacity to bind PSD95. Confocal microscopy analysis suggested that apical localization of TRPV4 required PSD95-TRPV4 interaction. Our data clearly suggest that formation of a complex between TRPV4 and PSD95 can regulate TRPV4 membrane localization. Both TRPV4 Ca2+ channel and its autophagy activity of 4d were reduced by more than 80% compared to those of the TRPV4 wild type. Our observation suggests that PSD95-TRPV4 complex plays crucial roles in routing TRPV4 to the apical plasma membrane and maintaining its authentic Ca2+ channel and biological function. CapsuleO_ST_ABSBackgroundC_ST_ABSTRPV4 contain putative PDZ tail motif (DAPL871). ResultsDeletion of TRPV4 tail PDZ motif fails to interact with PSD95 PDZ III domain. ConclusionTRPV4 tail is an authentic PDZ motif to interact with PSD95. SignificanceInteraction between TRPV4 and PSD95 requires for its proper biological functions.