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

First Author  Shang S Year  2016
Journal  J Cell Biol Volume  215
Issue  3 Pages  369-381
PubMed ID  27799370 Mgi Jnum  J:311640
Mgi Id  MGI:6203764 Doi  10.1083/jcb.201603081
Citation  Shang S, et al. (2016) Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons. J Cell Biol 215(3):369-381
abstractText  Transient receptor potential A1 (TRPA1) is a nonselective cation channel implicated in thermosensation and inflammatory pain. In this study, we show that TRPA1 (activated by allyl isothiocyanate, acrolein, and 4-hydroxynonenal) elevates the intracellular Ca(2+) concentration ([Ca(2+)]i) in dorsal root ganglion (DRG) neurons in the presence and absence of extracellular Ca(2+) Pharmacological and immunocytochemical analyses revealed the presence of TRPA1 channels both on the plasma membrane and in endolysosomes. Confocal line-scan imaging demonstrated Ca(2+) signals elicited from individual endolysosomes ("lysosome Ca(2+) sparks") by TRPA1 activation. In physiological solutions, the TRPA1-mediated endolysosomal Ca(2+) release contributed to approximately 40% of the overall [Ca(2+)]i rise and directly triggered vesicle exocytosis and calcitonin gene-related peptide release, which greatly enhanced the excitability of DRG neurons. Thus, in addition to working via Ca(2+) influx, TRPA1 channels trigger vesicle release in sensory neurons by releasing Ca(2+) from lysosome-like organelles.
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