期刊
JOURNAL OF CELL SCIENCE
卷 129, 期 20, 页码 3859-3867出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.190322
关键词
Ca2+; Lysosomes; TRP channels; Endoplasmic reticulum
类别
资金
- Biotechnology and Biological Sciences Research Council [BB/N01524X/1]
- Parkinson's UK [H-1202]
- BBSRC [BB/N01524X/1, BB/K000942/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [1676068, BB/N01524X/1, BB/K000942/1] Funding Source: researchfish
- Parkinson's UK [K-1107, K-1412, H-1202] Funding Source: researchfish
Transient receptor potential (TRP) mucolipins (TRPMLs), encoded by the MCOLN genes, are patho-physiologically relevant endolysosomal ion channels crucial for membrane trafficking. Several lines of evidence suggest that TRPMLs mediate localised Ca2+ release but their role in Ca2+ signalling is not clear. Here, we show that activation of endogenous and recombinant TRPMLs with synthetic agonists evoked global Ca2+ signals in human cells. These signals were blocked by a dominant-negative TRPML1 construct and a TRPML antagonist. We further show that, despite a predominant lysosomal localisation, TRPML1 supports both Ca2+ release and Ca2+ entry. Ca2+ release required lysosomal and ER Ca2+ stores suggesting that TRPMLs, like other endo-lysosomal Ca2+ channels, are capable of 'chatter' with ER Ca2+ channels. Our data identify new modalities for TRPML1 action.
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