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

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: 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

Posters

2015 - The backstage pass to study your favorite TRP channel

icon pap   Port-a-Patch and   icon pl   Patchliner and SyncroPatch 384PE (a predecessor model of SyncroPatch 384i) and   icon sp96   SyncroPatch 384PE poster, TRP Meeting 2015   logo pdf   (2.2 MB)

Publications

2019 - Purification of Functional Human TRP Channels Recombinantly Produced in Yeast

Icon Orbit Mini   Orbit mini publication in Cells (2019)

Authors:
Zhang L., Wang K., Klaerke D.A., Calloe K., Lowrey L., Pedersen P.A., Gourdon P., Gotfryd K.

2019 - Control of Lysosomal TRPML1 Channel Activity and Exosome Release by Acid Ceramidase in Mouse Podocytes

icon pap   Port-a Patch Publication in American Journal of Physiology Cell Physiology (2019)

Authors:
Li G., Huang D., Hong J., Bhat O.M., Yuan X., Li P.L.

2014 - A small molecule restores function to TRPML1 mutant isoforms responsible for mucolipidosis type IV

icon pap  Port-a-Patch publication in Nature Communications (2014)

Authors:
Chen C.C., Keller M., Hess M., Schiffmann R., Urban N., Wolfgardt A., Schaefer M., Bracher F., Biel M., Wahl-Schott C., Grimm C.

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