6aye

Structural highlights

Function

MCLN3_HUMAN Nonselective cation channel probably playing a role in the regulation of membrane trafficking events. Acts as Ca(2+)-permeable cation channel with inwardly rectifying activity (PubMed:18369318, PubMed:19497048, PubMed:19522758, PubMed:19885840). Mediates release of Ca(2+) from endosomes to the cytoplasm, contributes to endosomal acidification and is involved in the regulation of membrane trafficking and fusion in the endosomal pathway (PubMed:21245134). Does not seem to act as mechanosensory transduction channel in inner ear sensory hair cells. Proposed to play a critical role at the cochlear stereocilia ankle-link region during hair-bundle growth (By similarity). Involved in the regulation of autophagy (PubMed:19522758). Through association with GABARAPL2 may be involved in autophagosome formation possibly providing Ca(2+) for the fusion process (By similarity). Through a possible and probably tissue-specific heteromerization with MCOLN1 may be at least in part involved in many lysosome-dependent cellular events (PubMed:19885840). Possible heteromeric ion channel assemblies with TRPV5 show pharmacological similarity with TRPML3 (PubMed:23469151).[UniProtKB:Q8R4F0]^{[1] [2] [3] [4] [5] [6]}

References

1. ↑ Kim HJ, Li Q, Tjon-Kon-Sang S, So I, Kiselyov K, Soyombo AA, Muallem S. A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype. EMBO J. 2008 Apr 23;27(8):1197-205. doi: 10.1038/emboj.2008.56. Epub 2008 Mar 27. PMID:18369318 doi:http://dx.doi.org/10.1038/emboj.2008.56
2. ↑ Martina JA, Lelouvier B, Puertollano R. The calcium channel mucolipin-3 is a novel regulator of trafficking along the endosomal pathway. Traffic. 2009 Aug;10(8):1143-56. Epub 2009 Apr 29. PMID:19497048 doi:http://dx.doi.org/TRA935
3. ↑ Kim HJ, Soyombo AA, Tjon-Kon-Sang S, So I, Muallem S. The Ca(2+) channel TRPML3 regulates membrane trafficking and autophagy. Traffic. 2009 Aug;10(8):1157-67. doi: 10.1111/j.1600-0854.2009.00924.x. Epub 2009, May 11. PMID:19522758 doi:http://dx.doi.org/10.1111/j.1600-0854.2009.00924.x
4. ↑ Curcio-Morelli C, Zhang P, Venugopal B, Charles FA, Browning MF, Cantiello HF, Slaugenhaupt SA. Functional multimerization of mucolipin channel proteins. J Cell Physiol. 2010 Feb;222(2):328-35. doi: 10.1002/jcp.21956. PMID:19885840 doi:http://dx.doi.org/10.1002/jcp.21956
5. ↑ Lelouvier B, Puertollano R. Mucolipin-3 regulates luminal calcium, acidification, and membrane fusion in the endosomal pathway. J Biol Chem. 2011 Mar 18;286(11):9826-32. doi: 10.1074/jbc.M110.169185. Epub 2011, Jan 18. PMID:21245134 doi:http://dx.doi.org/10.1074/jbc.M110.169185
6. ↑ Guo Z, Grimm C, Becker L, Ricci AJ, Heller S. A novel ion channel formed by interaction of TRPML3 with TRPV5. PLoS One. 2013;8(2):e58174. doi: 10.1371/journal.pone.0058174. Epub 2013 Feb 28. PMID:23469151 doi:http://dx.doi.org/10.1371/journal.pone.0058174