Abstract
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.
Item Type: | Journal article |
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Faculties: | Chemistry and Pharmacy > Department of Pharmacy |
Research Centers: | Center for Integrated Protein Science Munich (CIPSM) |
Subjects: | 500 Science > 540 Chemistry |
ISSN: | 0021-9533 |
Language: | English |
Item ID: | 48554 |
Date Deposited: | 27. Apr 2018, 08:15 |
Last Modified: | 04. Nov 2020, 13:26 |