Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons

Abstract

The temperature-sensitive TRP channel, TRPA1, is known to mediate Na+ and Ca2+ influx at the plasma membrane of sensory neurons. In this study, the authors show that TRPA1 is also present on the lysosomal membrane and mediates lysosome Ca2+ release in dorsal root ganglion neurons.

TRPA1-dependent calcium transients and CGRP release in DRG neurons require extracellular calcium

“…The problem of contamination can be minimized by raising the EGTA concentration, for example from 1 to 10 mM, which reduces the relative error from 12% to 1% in case of an assumed 10 µM calcium contamination (Patton et al, 2004). Shang et al (2016) used glycylphenylalanine 2-naphtylamide (GPN) to osmotically disrupt the lysosomes, which caused a small cytosolic calcium transient (Fig. 3 C in Shang et al [2016]; and our Fig.…”

Cell biology in China: Focusing on the lysosome

“…A recent study from Zhuan Zhou's group at Peking University discovered that TRPA1, a known Ca 2+ channel on plasma membranes, also acts on the lysosomal membrane to release Ca 2+ in mouse DRG (dorsal root ganglion) neurons . TRPA1‐mediated lysosomal Ca 2+ release contributes to approximately 40% of the overall [Ca 2+ ] i rise and directly triggers vesicle exocytosis and neuropeptide release, thereby contributing significantly to TRPA1‐related pain sensation . Future studies are needed to understand the mechanisms of lysosomal TRPA1 activation and whether it functions coordinately with plasma membranous TRPA1.…”

Lysosomal Calcium in Neurodegeneration

“…Recently, Shang et al, reported the functional expression of TRPA1 in the peripheral lysosomes of dorsal root ganglion (DRG) neurons (Shang et al, 2016). Ca 2+ imaging studies has shown before that allyl isothiocyanate (AITC) could induce a TRPA1-dependent intracellular Ca 2+ release (Bandell et al, 2004; Jordt et al, 2004).…”