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The lysosomal Ca2+ release channel TRPML1 regulates lysosome size by activating calmodulin
| Content Provider | Scilit |
|---|---|
| Author | Cao, Qi Yang, Yiming Zhong, Xi Zoë Dong, Xian-Ping |
| Copyright Year | 2017 |
| Description | Journal: Journal of Biological Chemistry Intracellular lysosomal membrane trafficking, including fusion and fission, is crucial for cellular homeostasis and normal cell function. Both fusion and fission of lysosomal membrane are accompanied by lysosomal $Ca^{2+}$ release. We recently have demonstrated that the lysosomal $Ca^{2+}$ release channel P2X4 regulates lysosome fusion through a calmodulin (CaM)-dependent mechanism. However, the molecular mechanism underlying lysosome fission remains uncertain. In this study, we report that enlarged lysosomes/vacuoles induced by either vacuolin-1 or P2X4 activation are suppressed by up-regulating the lysosomal $Ca^{2+}$ release channel transient receptor potential mucolipin 1 (TRPML1) but not the lysosomal $Na^{+}$ release channel two-pore channel 2 (TPC2). Activation of TRPML1 facilitated the recovery of enlarged lysosomes/vacuoles. Moreover, the effects of TRPML1 on lysosome/vacuole size regulation were eliminated by $Ca^{2+}$ chelation, suggesting a requirement for TRPML1-mediated $Ca^{2+}$ release. We further demonstrate that the prototypical $Ca^{2+}$ sensor CaM is required for the regulation of lysosome/vacuole size by TRPML1, suggesting that TRPML1 may promote lysosome fission by activating CaM. Given that lysosome fission is implicated in both lysosome biogenesis and reformation, our findings suggest that TRPML1 may function as a key lysosomal $Ca^{2+}$ channel controlling both lysosome biogenesis and reformation. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5437247/pdf http://www.jbc.org/content/292/20/8424.full.pdf |
| Ending Page | 8435 |
| Page Count | 12 |
| Starting Page | 8424 |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| DOI | 10.1074/jbc.m116.772160 |
| Journal | Journal of Biological Chemistry |
| Issue Number | 20 |
| Volume Number | 292 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2017-05-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Biological Chemistry Biochemistry and Molecular Biology Cell Biology Calcium Channel Calmodulin (cam) Lysosomal Ca2+ Membrane Trafficking |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
