TRPV1 expression‐dependent initiation and regulation of filopodia

Abstract

Transient receptor potential vanilloid subtype 1 (TRPV1), a non-selective cation channel, is present endogenously in dorsal root ganglia (DRG) neurons. It is involved in the recognition of various pain producing physical and chemical stimuli. In this work, we demonstrate that expression of TRPV1 induces neurite-like structures and filopodia and that the expressed protein is localized at the filopodial tips. Exogenous expression of TRPV1 induces filopodia both in DRG neuron-derived F11 cells and in non-neuronal cells, such as HeLa and human embryonic kidney (HEK) cells. We find that some of the TRPV1 expression-induced filopodia contain microtubules and microtubule-associated components, and establish cell-to-cell extensions. Using live cell microscopy, we demonstrate that the filopodia are responsive to TRPV1-specific ligands. But both, initiation and subsequent cell-to-cell extension formation, is independent of TRPV1 channel activity. The N-terminal intracellular domain of TRPV1 is sufficient for filopodial structure initiation while the C-terminal cytoplasmic domain is involved in the stabilization of microtubules within these structures. In addition, exogenous expression of TRPV1 results in altered cellular distribution and in enhanced endogenous expression of non-conventional myosin motors, namely myosin IIA and myosin IIIA. These data indicate a novel role of TRPV1 in the regulation of cellular morphology and cellular contact formation.

Right time - right location - right move: TRPs find motors for common functions

“…12 Similarly, TRPV4 is also located at the filopodial and lamelipodial structures; 13 and in a same manner, endogenous TRPV4 is also present in the cholangiocyte cilia.…”

“…12 Interestingly, these heads often contain negligible amounts of F-actin but accumulate TRPV1 there. 12 This phenotype and localization of TRPV1 resemble well with the dominant-negative effect of non-conventional myosin motors.…”

“…12 Interestingly, these heads often contain negligible amounts of F-actin but accumulate TRPV1 there. 12 This phenotype and localization of TRPV1 resemble well with the dominant-negative effect of non-conventional myosin motors. This is mainly due to the fact that overexpression of myosin II, III, V, X and XV is known to induce filopodial structure of same morphology, and these myosin motors also localize at the bulbous head regions.…”

Transient Receptor Potential Channels: What is happening? Reflections in the wake of the 2009 TRP meeting, Karolinska Institutet, Stockholm

“…[136][137][138][139] By regulating Ca 2+ and other second messengers, the TRP channels may contribute to the survival and differentiation of cells and tissues, especially in the early embryonic stages. Indeed, expression of some TRP channels, like TRPV1 in the early embryonic stages has been reported, 136,140 and the expression of several TRP channels co-relate with the differentiation of the stem cells. 141 Being non-selective Ca 2+ channels, TRP channels can regulate the Ca 2+ -signaling events including Ca 2+ -waves.…”

Crosstalk from cAMP to ERK1/2 emerges during postnatal maturation of nociceptive neurons and is maintained during aging

“…Proteins defining nociceptor functionality appear at different times during development. While the polymodal ion channel TRPV1 is already expressed by embryonic day (E)13 (Goswami and Hucho, 2007;Hjerling-Leffler et al, 2007), voltage-gated sodium channels such as Na V 1.7 (also known as SCN9A) are upregulated postnatally (Benn et al, 2001;Felts et al, 1997). In contrast to changes in ion channel or growth factor receptor expression, an analysis of when during development the expression of intracellular sensitization signaling components such as PKA-RIIβ and CaMKIIα is established, how this relates to classical markers of nociceptors such as Nav1.8 and TRPV1, and how this develops in senescent animals, is currently missing.…”