TRPML3
TRPML3 is an endolysosomal Ca2+-permeable cation channel that regulates endocytosis, membrane trafficking, and autophagy[1]. Mechanistically, TRPML3 functions as a PI3P effector on phagophores, releasing Ca2+ required for autophagosome biogenesis[2]. In disease models, gain-of-function Trpml3 mutations cause deafness, circling behavior, and pigmentation defects in mice[3]. Compared with related isoforms, TRPML3 shows distinct low-pH inhibition and structural gating, while ML-SA1 opens the S6 gate in agonist-activated human TRPML3[4]. Small-molecule TRPML3 activators identified by high-throughput screening provide tools for studying channel activity, autophagy, and endolysosomal trafficking[5].
References:
- [1]. Kim HJ, et al. The Ca(2+) channel TRPML3 regulates membrane trafficking and autophagy. Traffic. 2009 Aug;10(8):1157-67. [Content Brief]
- [2]. Kim SW, et al. The intracellular Ca2+ channel TRPML3 is a PI3P effector that regulates autophagosome biogenesis. Proc Natl Acad Sci U S A. 2022 Oct 25;119(43):e2200085119. [Content Brief]
- [3]. Spix B, et al. Whole-body analysis of TRPML3 (MCOLN3) expression using a GFP-reporter mouse model reveals widespread expression in secretory cells and endocrine glands. PLoS One. 2022 Dec 15;17(12):e0278848. [Content Brief]
- [4]. Zhou X, et al. Cryo-EM structures of the human endolysosomal TRPML3 channel in three distinct states. Nat Struct Mol Biol. 2017 Dec;24(12):1146-1154. [Content Brief]
- [5]. Grimm C, et al. Small molecule activators of TRPML3. Chem Biol. 2010 Feb 26;17(2):135-48. [Content Brief]
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TRPML3 Related Products (4)
Related Products (4)
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ML-SI3
0 ImagesSynonyms: ML-SI3 (cis/trans mix)ML-SI3 is a mixture of cis/trans ML-SI3 (HY-139426A), which is a TRPML1/2 channel inhibitor with IC50s of 4.7 μM and 1.7 μM, respectively. ML-SI3 also inhibits lysosomal calcium efflux and blocks downstream TRPML1-mediated autophagy. The cis/trans ML-SI3 (HY-139426A) components of ML-SI3 are TRPML2 activators with EC50s of 3.3 μM and 9.4 μM, respectively.
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(rel)-ML-SI3
0 ImagesSynonyms: trans-ML-SI3
