TRPML1 | Transient Receptor Potential Cation Channel Subfamily ML Member 1

Mucolipin-1, also called TRMPL1 ((transient receptor potential cation channel, mucolipin subfamily, member 1) is a lysosomal monovalent cation/Ca²⁺ channel: It is proposed to play a major role in Ca²⁺ 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. The channel function is transiently modulated by changes in Ca²⁺, and inhibited by a reduction of pH.

Gene:
MCOLN1

Human Protein:
UniProt Q8IZK6

Tissue:
The transmembrane protein localizes to intracellular vesicular membranes including lysosomes, it is widely expressed in adult and fetal tissues, highest expression level in adrenal gland

Function/ Application:
TRPML1 functions in the late endocytic pathway and in the regulation of lysosomal exocytosis. The channel is permeable to Ca²⁺, Na²⁺, K²⁺, and H²⁺, as well as diverse metal ions as Fe²⁺, Zn²⁺, Ni²⁺, and is modulated by changes in Ca²⁺ concentration. TRPML1 is believed to channel iron ions across the endosome/lysosome membrane into the cell and so its malfunction causes cellular iron deficiency. TrpML1 is probably involved in Zn²⁺ uptake into lysosomes and required for efficient uptake of large particles in macrophages in which Ca²⁺ release from the lysosomes triggers lysosomal exocytosis. The channel seems to act as lysosomal active oxygen species (ROS) sensor involved in ROS-induced TFEB activation and autophagy

Pathology:
Mucolipidosis type IV, Niemann-Pick disease , leukomalacia, yunis-varon syndrome, cerebral palsy, ataxic, autosomal recessive

Accessory subunits:
Can heterooligomerize with MCOLN2 (TRPML2) or MCOLN3 (TRPML3)

Interaction:
PDCD6, TMEM163, LAPTM4B, TPC1, TPC2

Modulator:
In lysosomes activated by PtdIns(3,5)P2 (Phosphatidylinositol 3,5-bisphosphate) and at the plasma membrane inhibited by PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate). activators: ML SA1, MK6-83, SF-22, SF-51, blocker: La^3+,

Assays:
Patch Clamp: whole lysosome recording

Recommended Reviews:
International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels., Pharmacol Rev 55(4):591-6 Clapham, et al. 2003