Transient Receptor Potential Vanilloid 4 inhibition regulates microglial cytoskeleton dynamics in vitro

Abstract

Ramified microglia use their branches to actively scan the healthy central nervous system, a process regulated by intracellular calcium fluctuations. It has been demonstrated that local calcium increases can be initiated by both chemoattractant signal transduction and membrane tension, posing the mechanosensitive members of the Transient Receptor Potential (TRP) superfamily of cation channels as potential transducers of mechanical force into intracellular calcium fluctuations. Indeed, it has recently been shown that the calcium permeable and mechanosensitive channel TRP Vanilloid 4 (TRPV4) contributes to microglial motility. However, it is still unknown how TRPV4 regulates the microglial cytoskeleton. Using high-end live microscopy techniques, this study showed that inhibition of TRPV4 decreases actin and tubulin cytoskeleton dynamics of cultured primary mouse microglia. Furthermore, inhibition resulted in loss of their extensive ramifications. Hereby, this study suggests that TRPV4 is crucial for proper microglial motility and surveillance of the central nervous system.