title: Intracellular TRPA1 mediates Ca2+ release from lysosomes in dorsal root ganglion neurons.
abstract: 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 Ca2+concentration ([Ca2+]i) in dorsal root ganglion (DRG) neurons in the presence and absence of extracellular Ca2+Pharmacological and immunocytochemical analyses revealed the presence of TRPA1 channels both on the plasma membrane and in endolysosomes. Confocal line-scan imaging demonstrated Ca2+signals elicited from individual endolysosomes ("lysosome Ca2+sparks") by TRPA1 activation. In physiological solutions, the TRPA1-mediated endolysosomal Ca2+release contributed to ∼40% of the overall [Ca2+]irise 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 Ca2+influx, TRPA1 channels trigger vesicle release in sensory neurons by releasing Ca2+from lysosome-like organelles.
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.|Laboratory Animal Center, Peking University, Beijing 100871, China.|School of Life Science, Peking University, Beijing 100871, China.
authors: Shujiang
authors: S
authors: Shang
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Feipeng
authors: F
authors: Zhu
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Bin
authors: B
authors: Liu
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Zuying
authors: Z
authors: Chai
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Qihui
authors: Q
authors: Wu
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Meiqin
authors: M
authors: Hu
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Yuan
authors: Y
authors: Wang
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Rong
authors: R
authors: Huang
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Xiaoyu
authors: X
authors: Zhang
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Xi
authors: X
authors: Wu
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Lei
authors: L
authors: Sun
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Yeshi
authors: Y
authors: Wang
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Li
authors: L
authors: Wang
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Huadong
authors: H
authors: Xu
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Sasa
authors: S
authors: Teng
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Bing
authors: B
authors: Liu
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China.
authors: Lianghong
authors: L
authors: Zheng
authors: School of Life Science, Peking University, Beijing 100871, China.
authors: Chen
authors: C
authors: Zhang
authors: Institute for Biomedical Science of Pain, Capital Medical University, Beijing 100069, China.
authors: Fukang
authors: F
authors: Zhang
authors: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030.
authors: Xinghua
authors: X
authors: Feng
authors: Laboratory Animal Center, Peking University, Beijing 100871, China.
authors: Desheng
authors: D
authors: Zhu
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China zzhou@pku.edu.cn michael.x.zhu@uth.tmc.edu tao.liu06@gmail.com changhewang@pku.edu.cn.
authors: Changhe
authors: http://orcid.org/0000-0002-5902-2277
authors: C
authors: Wang
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China zzhou@pku.edu.cn michael.x.zhu@uth.tmc.edu tao.liu06@gmail.com changhewang@pku.edu.cn.
authors: Tao
authors: T
authors: Liu
authors: Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center at Houston, Houston, TX 77030 zzhou@pku.edu.cn michael.x.zhu@uth.tmc.edu tao.liu06@gmail.com changhewang@pku.edu.cn.
authors: Michael X
authors: MX
authors: Zhu
authors: State Key Laboratory of Membrane Biology and Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Institute of Molecular Medicine and Peking-Tsinghua Center for Life Sciences and PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing 100871, China zzhou@pku.edu.cn michael.x.zhu@uth.tmc.edu tao.liu06@gmail.com changhewang@pku.edu.cn.
authors: Zhuan
authors: http://orcid.org/0000-0001-9048-6638
authors: Z
authors: Zhou
mesh_terms: D000171:Acrolein; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005089:Exocytosis; D005727:Ganglia, Spinal / Q000378:metabolism*; D006930:Hyperalgesia / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism*; D015640:Ion Channel Gating; D017879:Isothiocyanates; D008247:Lysosomes / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D012996:Solutions; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000378:metabolism*
chemical_list: D017879:Isothiocyanates; D009479:Neuropeptides; D012996:Solutions; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; D000171:Acrolein; C004471:allyl isothiocyanate; D015740:Calcitonin Gene-Related Peptide; D002118:Calcium