TRP mucolipins (TRPMLs) are patho-physiologically relevant endo-lysosomal ion channels critical 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 evoke 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.
- Received April 15, 2016.
- Accepted August 19, 2016.
- © 2016. Published by The Company of Biologists Ltd
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