MCOLN1 explained

Mucolipin-1 also known as TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) is a protein that in humans is encoded by the MCOLN1 gene.^[1] It is a member of the small family of the TRPML channels, a subgroup of the large protein family of TRP ion channels.

TRPML1 is a 65 kDa protein associated with mucolipidosis type IV. Its predicted structure includes six transmembrane domains, a transient receptor potential (TRP) cation-channel domain, and an internal channel pore.^[2] TRPML1 is believed to channel iron ions across the endosome/lysosome membrane into the cell and so its malfunction causes cellular iron deficiency.^[3] It is important in lysosome function and plays a part in processes such as vesicular trafficking, exocytosis and autophagy.^{[4] [5]}

Ligands

Agonists

• ML-SA1
• MK6-83^[6]

See also

• transient receptor potential cation channel, mucolipin subfamily, member 2 (MCOLN2)
• transient receptor potential cation channel, mucolipin subfamily, member 3 (MCOLN3)
• mucolipidosis type IV
• TRPML

External links

• GeneReviews/NIH/NCBI/UW entry on Mucolipidosis IV

Notes and References

1. Clapham DE, Julius D, Montell C, Schultz G . International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels . Pharmacol. Rev. . 57 . 4 . 427–50 . December 2005 . 16382100 . 10.1124/pr.57.4.6 . 17936350 .
2. Venugopal B, Browning MF, Curcio-Morelli C, Varro A, Michaud N, Nanthakumar N, Walkley SU, Pickel J, Slaugenhaupt SA . Neurologic, gastric, and pathologies in a murine model of mucolipidosis type IV . Am. J. Hum. Genet. . 81 . 5 . 1070–83 . November 2007 . 17924347 . 2265643 . 10.1086/521954 .
3. Dong X, Cheng X, Mills E, Delling M, Wang F, Kurz T, Xu H . The Type IV Mucolipidosis-Associated Protein TRPML1 is an Endo-lysosomal Iron Release Channel . Nature . 2008 . 10.1038/nature07311 . 455 . 992–6 . 18794901 . 7215. 4301259 . 2008Natur.455..992D .
4. Book: Wang W, Zhang X, Gao Q, Xu H . Mammalian Transient Receptor Potential (TRP) Cation Channels . TRPML1: an ion channel in the lysosome . Handbook of Experimental Pharmacology . 222 . 631–45 . 2014 . 24756723 . 10.1007/978-3-642-54215-2_24 . 978-3-642-54214-5 .
5. Di Paola S, Scotto-Rosato A, Medina DL . TRPML1: The Ca(2+)retaker of the lysosome . Cell Calcium . 69 . 112–121 . January 2018 . 28689729 . 10.1016/j.ceca.2017.06.006 .
6. Schmiege P, Fine M, Blobel G, Li X . Human TRPML1 channel structures in open and closed conformations . Nature . 550 . 7676 . 366–370 . October 2017 . 29019983 . 5920536 . 10.1038/nature24036 . 2017Natur.550..366S .