TRPML1 | Transient Receptor Potential Cation Channel Subfamily ML Member 1
Family:
Transient receptor potential channels
Subgroups:
TRPC (TRPC1–TRPC7), TRPV (TRPV1-TRPV6), TRPA1, TRPM (TRPM1–TRPM8), TRPP (TRPP1–TRPP3, PKD1, PKDREJ, PKDL1–PKDL3), TRPML (TRPML1–TRPML3), TRPN
Topology:
Most TRP channels are composed of 6 transmembrane domains (helices) with intracellular N- and C-termini, non-selectively permeable to various cations
TRPML1 (Mucolipin-1): Background information
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+, Na+, K+, and H+, 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: La3+,
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