5ye5

Structural highlights

Function

[MCLN1_MOUSE] Nonselective cation channel probably playing a role in the regulation of membrane trafficking events and of metal homeostasis. Proposed to play a major role in Ca(2+) release from late endosome and lysosome vesicles to the cytoplasm, which is important for many lysosome-dependent cellular events, including the fusion and trafficking of these organelles, exocytosis and autophagy. Required for efficient uptake of large particles in macrophages in which Ca(2+) release from the lysosomes triggers lysosomal exocytosis. May also play a role in phagosome-lysosome fusion (PubMed:23993788). Involved in lactosylceramide trafficking indicative for a role in the regulation of late endocytic membrane fusion/fission events. By mediating lysosomal Ca(2+) release is involved in regulation of mTORC1 signaling and in mTOR/TFEB-dependent lysosomal adaptation to environmental cues such as nutrient levels (PubMed:25733853). Seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS-induced TFEB activation and autophagy (By similarity). Functions as a Fe(2+) permeable channel in late endosomes and lysosomes. Proposed to play a role in zinc homeostasis probably implicating its association with TMEM163 (By similarity). In adaptive immunity, TRPML2 and TRPML1 may play redundant roles in the function of the specialized lysosomes of B cells (PubMed:17050035).[UniProtKB:Q9GZU1]^{[1] [2] [3]} May contribute to cellular lipase activity within the late endosomal pathway or at the cell surface which may be involved in processes of membrane reshaping and vesiculation, especially the growth of tubular structures. However, it is not known, whether it conveys the enzymatic activity directly, or merely facilitates the activity of an associated phospholipase.[UniProtKB:Q9GZU1]

References

1. ↑ Song Y, Dayalu R, Matthews SA, Scharenberg AM. TRPML cation channels regulate the specialized lysosomal compartment of vertebrate B-lymphocytes. Eur J Cell Biol. 2006 Dec;85(12):1253-64. Epub 2006 Oct 16. PMID:17050035 doi:http://dx.doi.org/10.1016/j.ejcb.2006.08.004
2. ↑ Samie M, Wang X, Zhang X, Goschka A, Li X, Cheng X, Gregg E, Azar M, Zhuo Y, Garrity AG, Gao Q, Slaugenhaupt S, Pickel J, Zolov SN, Weisman LS, Lenk GM, Titus S, Bryant-Genevier M, Southall N, Juan M, Ferrer M, Xu H. A TRP channel in the lysosome regulates large particle phagocytosis via focal exocytosis. Dev Cell. 2013 Sep 16;26(5):511-24. doi: 10.1016/j.devcel.2013.08.003. Epub 2013 , Aug 29. PMID:23993788 doi:http://dx.doi.org/10.1016/j.devcel.2013.08.003
3. ↑ Wang W, Gao Q, Yang M, Zhang X, Yu L, Lawas M, Li X, Bryant-Genevier M, Southall NT, Marugan J, Ferrer M, Xu H. Up-regulation of lysosomal TRPML1 channels is essential for lysosomal adaptation to nutrient starvation. Proc Natl Acad Sci U S A. 2015 Mar 17;112(11):E1373-81. doi:, 10.1073/pnas.1419669112. Epub 2015 Mar 2. PMID:25733853 doi:http://dx.doi.org/10.1073/pnas.1419669112
4. ↑ Zhang S, Li N, Zeng W, Gao N, Yang M. Cryo-EM structures of the mammalian endo-lysosomal TRPML1 channel elucidate the combined regulation mechanism. Protein Cell. 2017 Nov;8(11):834-847. doi: 10.1007/s13238-017-0476-5. Epub 2017, Sep 21. PMID:28936784 doi:http://dx.doi.org/10.1007/s13238-017-0476-5