TRPML3 | Transient Receptor Potential channels | IUPHAR/BPS Guide to PHARMACOLOGY

TRPML3

Target id: 503

Nomenclature: TRPML3

Family: Transient Receptor Potential channels

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for TRPML3 in GtoImmuPdb

Gene and Protein Information
Species TM P Loops AA Chromosomal Location Gene Symbol Gene Name Reference
Human 6 1 553 1p22.3 MCOLN3 mucolipin 3 5
Mouse 6 1 553 3 H2 Mcoln3 mucolipin 3 5
Rat 6 1 553 2q44 Mcoln3 mucolipin 3
Previous and Unofficial Names
Mucolipin3
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Cryo-electron microscopy structure of a TRPML3 ion channel
PDB Id:  5W3S
Resolution:  2.94Å
Species:  Monkey
References:  11
Associated Proteins
Heteromeric Pore-forming Subunits
Name References
TRPML1 3,22
TRPML2 3,22
Auxiliary Subunits
Name References
Not determined
Other Associated Proteins
Name References
Hsc70 (potentially) 19
TPC2 21
Functional Characteristics
TRPML3Va: γ = 49 pS at very negative holding potentials with monovalent cations as charge carrier; conducts Na+ > K+ > Cs+ with maintained current in the presence of Na+, conducts Ca2+ and Mg2+, but not Fe2+, impermeable to protons; inwardly rectifying Wild type TRPML3: γ = 59 pS at negative holding potentials with monovalent cations as charge carrier; conducts Na+ > K+ > Cs+ and Ca2+ (PCa/PK ≅ 350), slowly inactivates in the continued presence of Na+ within the extracellular (extracytosolic) solution; outwardly rectifying
Ion Selectivity and Conductance Comments
The varitint-waddler mutation of mouse TRPML3 (A419P or Va mutation) is a non-selective inwardly rectifying ion channel permeant to Na+, K+, Cs+, Mg2+ and Ca2+, but does not conduct protons [8,20].
Ion selectivity rank order: Na+~ K+> Cs+ (pS=50 at negative voltages, [16,20] measured using the activation mutation A419P; Ca2+> Na+>K+>>Cs+>Sr2+ or Ba2+ or Mg2+ [13].

Wild type TRPML3 appears to primarily span intracellular membranes of lysosomes and endosomes. The current attributed to this channel in [16] may result from other plasma membrane TRP channels.
Voltage Dependence Comments
Strong inwardly rectifying, activation only at negative voltages: instantaneous but not time-dependent [20].
Activators (Human)
TRPML3Va: Constitutively active, current inhibited by extracellular acidification (equivalent to intralysosomal acidicification)
Wild type TRPML3: Activated by Na+-free extracellular (extracytosolic) solution and membrane depolarization, current inhibited by extracellular acidification (equivalent to intralysosomal acidicification)

Download all structure-activity data for this target as a CSV file

Activators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
SF-11 Hs Activation 6.6 pEC50 - - 10
pEC50 6.6 (EC50 2.6x10-7 M) [10]
SF-21 Hs Activation 6.3 pEC50 - - 10
pEC50 6.3 (EC50 4.5x10-7 M) [10]
SN-1 Hs Activation 6.1 pEC50 - - 10
pEC50 6.1 (EC50 8.8x10-7 M) [10]
SN-2 Hs Activation 6.0 pEC50 - - 10
pEC50 6.0 (EC50 1.1x10-6 M) [10]
MK6-83 Hs Activation - - - - 7
[7]
Description: Measurement of intracellular calcium levels (fura-2 ratios F340/F380)
Activator Comments
Phosphatidyl (3,5) inositol bisphosphate [13] and ML SA1 [17] are both activators of TRPML3. Other synthetic activators of TRPML3 are SF-22, SF-23, SF-24, SF-31, SF-32, SF-33, SF-41, SF-51, SF-61, SF-71 and SF-81 [9].
Gating Inhibitor Comments
High Na+ concentration (140mM, [9,12-13]), H+ (pH 6.42, extracellular or luminal side, [13]) and high concentrations of verapamil (1mM, [20]) all block TRPML3 activation.
Channel Blockers
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Concentration range (M) Holding voltage (mV) Reference
Gd3+ Mm Antagonist 4.7 pIC50 - -80.0 16
pIC50 4.7 (IC50 2x10-5 M) [16]
Holding voltage: -80.0 mV
Tissue Distribution
Skin melanocytes
Species:  Mouse
Technique:  Immunohistochemistry
References:  20
High level of expression in brain, thymus, lung, kidney and spleen
Expression level:  High
Species:  Mouse
Technique:  RT-PCR
References:  2
Strong expression in cochlear and vestibular sensory hair cells, marginal cells of the stria vascularis, Reissner's membrane, and weaker expression in cells of spiral limbus and Hensen's and Claudius's cells. Also expressed in vomeronasal and olfactory receptor neurons.
Species:  Mouse
Technique:  Immunohistochemistry, in situ hybridisation, RT-PCR
References:  1,5,16
Functional Assays
Ca2+ imaging (human and mouse)
Species:  Human
Tissue:  HEK293T cells expressing TRPML3 or TRPML3-Va channels
Response measured:  Constitutive or agonist-induced Ca2+ influx
References:  9-10,20
Whole-endolysosome patch-clamp. In the whole-endolysosome configuration, “inward” currents indicate the cations flowing out of the lumen to the cytoplasm.
Species:  Mouse
Tissue:  HEK293 or COS1 cells transfected with TRPML3 or TRPML3-Va
Response measured:  TRPML3 currents; activation by PI(3,5)P2
References:  6
Whole-cell recordings (human or mouse)
Species:  Human
Tissue:  HEK293T cells expressing TRPML3 or TRPML3-Va channels
Response measured:  Constitutive whole cell currents (for TRPML3-Va) or currents activated by synthetic agonists or Na+ removal followed by re-addition.
References:  8-9,12-13,16-17,20
Single-channel recordings (human or mouse)
Species:  Human
Tissue:  CL4 cells or HEK293 cells
Response measured:  Currents from TRPML3-Va (A419P)
References:  16,20
Physiological Functions
Putative heteromerisation with TRPML1 or TRPML2 affects its localisation to lysosomes.
Species:  Human
Tissue:  HEK cells.
References:  18
Autophagy
Species:  Human
Tissue:  HeLa cells
References:  14-15
Endolysosomal pH homeostasis
Species:  Human
Tissue:  HeLa cells
References:  15
Membrane trafficking along endolysosomal pathways
Species:  Human
Tissue:  HeLa cells
References:  14-15
Gain-of-function mutations of TRPML3 lead to defective function of hair cells
Species:  Mouse
Tissue:  Hair cells
References:  5,8,16
Gain-of-function mutations of TRPML3 lead to melanocyte loss
Species:  Mouse
Tissue:  Melanocytes
References:  5,20
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0004738 abnormal brainstem auditory evoked potential PMID: 12209292 
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
B6C3Fe-a/a Hoxa13 Mcoln3/J
MGI:1890500  MP:0004738 abnormal brainstem auditory evoked potential PMID: 12209292 
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0002622 abnormal cochlear hair cell morphology
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0004249 abnormal crista ampullaris morphology
Mcoln3Va Mcoln3Va/Mcoln3Va
mixed
MGI:1890500  MP:0004249 abnormal crista ampullaris morphology
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0003312 abnormal locomotor coordination
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0003312 abnormal locomotor coordination
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0001386 abnormal maternal nurturing
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0001386 abnormal maternal nurturing
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
Not Specified
MGI:1890500  MP:0002095 abnormal skin pigmentation PMID: 4557539 
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0000048 abnormal stria vascularis
Mcoln3Va Mcoln3Va/Mcoln3Va
mixed
MGI:1890500  MP:0000048 abnormal stria vascularis
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0002856 abnormal vestibular ganglion morphology
Mcoln3Va Mcoln3Va/Mcoln3Va
mixed
MGI:1890500  MP:0002856 abnormal vestibular ganglion morphology
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0003703 abnormal vestibulocochlear ganglion morphology
Mcoln3Va Mcoln3Va/Mcoln3Va
mixed
MGI:1890500  MP:0003703 abnormal vestibulocochlear ganglion morphology
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0004763 absent brainstem auditory evoked potential PMID: 12209292 
Mcoln3Va-J Mcoln3Va-J/?
involves: C3HeB/FeJLe * C57BL/6J
MGI:1890500  MP:0004763 absent brainstem auditory evoked potential PMID: 12209292 
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
B6C3Fe-a/a Hoxa13 Mcoln3/J
MGI:1890500  MP:0004763 absent brainstem auditory evoked potential PMID: 12209292 
Mcoln3Va-J Mcoln3Va-J/?
involves: A/J * C57BL/6J
MGI:1890500  MP:0004763 absent brainstem auditory evoked potential PMID: 12209292 
Mcoln3Va-J Mcoln3Va-J/?
involves: C57BL/6J * DBA/2J
MGI:1890500  MP:0004763 absent brainstem auditory evoked potential PMID: 12209292 
Mcoln3Va-J Mcoln3Va-J/?
involves: BALB/cByJ * C57BL/6J
MGI:1890500  MP:0004763 absent brainstem auditory evoked potential PMID: 12209292 
Mcoln3Va-J Mcoln3Va-J/?
involves: C57BL/6J * CZECHII/EiJ
MGI:1890500  MP:0004763 absent brainstem auditory evoked potential PMID: 12209292 
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
Not Specified
MGI:1890500  MP:0000373 belly spot PMID: 4557539 
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
B6C3Fe-a/a Hoxa13 Mcoln3/J
MGI:1890500  MP:0000373 belly spot PMID: 12209292 
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0001394 circling
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0001394 circling
Mcoln3Va-J|Mcoln3Va Mcoln3Va/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0001394 circling PMID: 4557539 
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0002857 cochlear ganglion degeneration
Mcoln3Va Mcoln3Va/Mcoln3Va
mixed
MGI:1890500  MP:0002857 cochlear ganglion degeneration
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0004362 cochlear hair cell degeneration
Mcoln3Va Mcoln3Va/Mcoln3Va
mixed
MGI:1890500  MP:0004362 cochlear hair cell degeneration
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0001967 deafness PMID: 12209292 
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0001967 deafness
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
Not Specified
MGI:1890500  MP:0001967 deafness PMID: 4557539 
Mcoln3Va-J Mcoln3Va-J/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0001967 deafness PMID: 4557539 
Mcoln3Va-J|Mcoln3Va Mcoln3Va/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0001967 deafness PMID: 4557539 
Mcoln3Va-J|Mcoln3Va Mcoln3Va/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0001265 decreased body size PMID: 4557539 
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0004765 decreased brainstem auditory evoked potential PMID: 12209292 
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
B6C3Fe-a/a Hoxa13 Mcoln3/J
MGI:1890500  MP:0004765 decreased brainstem auditory evoked potential PMID: 12209292 
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0003150 detached tectorial membrane
Mcoln3Va Mcoln3Va/Mcoln3Va
mixed
MGI:1890500  MP:0003150 detached tectorial membrane
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0000371 diluted coat color PMID: 12209292 
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
Not Specified
MGI:1890500  MP:0000371 diluted coat color PMID: 4557539 
Mcoln3Va-J Mcoln3Va-J/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0000371 diluted coat color PMID: 4557539 
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
B6C3Fe-a/a Hoxa13 Mcoln3/J
MGI:1890500  MP:0000371 diluted coat color PMID: 12209292 
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0004591 enlarged tectorial membrane
Mcoln3Va Mcoln3Va/Mcoln3Va
mixed
MGI:1890500  MP:0004591 enlarged tectorial membrane
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0002939 head spot PMID: 12209292 
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
B6C3Fe-a/a Hoxa13 Mcoln3/J
MGI:1890500  MP:0002939 head spot PMID: 12209292 
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0005307 head tossing
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0005307 head tossing
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0001399 hyperactivity
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0001399 hyperactivity
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0001405 impaired coordination
Mcoln3Va Mcoln3Va/Mcoln3Va
mixed
MGI:1890500  MP:0001523 impaired righting response
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
mixed
MGI:1890500  MP:0001522 impaired swimming
Mcoln3Va-J|Mcoln3Va Mcoln3Va/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0001522 impaired swimming PMID: 4557539 
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0001401 jumpy
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0001401 jumpy
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0000421 mottled coat PMID: 12209292 
Mcoln3Va-J Mcoln3Va-J/Mcoln3Va-J
B6C3Fe-a/a Hoxa13 Mcoln3/J
MGI:1890500  MP:0000421 mottled coat PMID: 12209292 
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
Not Specified
MGI:1890500  MP:0005175 non-pigmented tail tip PMID: 4557539 
Mcoln3Va-J|Mcoln3Va Mcoln3Va/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0002082 postnatal lethality PMID: 4557539 
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0002080 prenatal lethality
Mcoln3Va Mcoln3Va/Mcoln3Va
mixed
MGI:1890500  MP:0002080 prenatal lethality
Mcoln3Va-J Mcoln3Va-J/Mcoln3Va-J
B6.Cg-Mcoln3
MGI:1890500  MP:0002080 prenatal lethality PMID: 12209292 
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0001921 reduced fertility
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0001921 reduced fertility
Mcoln3Va-J|Mcoln3Va Mcoln3Va/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0001921 reduced fertility PMID: 4557539 
Mcoln3Va-J|Mcoln3Va Mcoln3Va/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0001408 stereotypic behavior
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0002826 tonic seizures
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0002826 tonic seizures
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0005366 variegated coat color
Mcoln3Va Mcoln3Va/Mcoln3Va
involves: C57BL * C57BR
MGI:1890500  MP:0005366 variegated coat color
Mcoln3+|Mcoln3Va-J Mcoln3Va-J/Mcoln3+
Not Specified
MGI:1890500  MP:0005366 variegated coat color
Mcoln3Va-J Mcoln3Va-J/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0005366 variegated coat color
Mcoln3Va-J|Mcoln3Va Mcoln3Va/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0005366 variegated coat color
Mcoln3+|Mcoln3Va Mcoln3Va/Mcoln3+
involves: C57BL * C57BR
MGI:1890500  MP:0002938 white spotting PMID: 12209292 
Mcoln3Va-J Mcoln3Va-J/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0002938 white spotting PMID: 4557539 
Mcoln3Va-J|Mcoln3Va Mcoln3Va/Mcoln3Va-J
Not Specified
MGI:1890500  MP:0002938 white spotting PMID: 4557539 
Gene Expression and Pathophysiology
Overexpression
Tissue or cell type:  ARPE19 cells
Pathophysiology:  Higher endosomal pH
Species:  Human
Technique: 
References:  15
Biologically Significant Variants
Type:  Missense mutation
Species:  Mouse
Description:  Mutation of alanine to proline at position 419 leads to the varitint-waddler phenotype. Mice heterozygous for the varitint-waddler mutation are deaf and show varying degrees of circling behavior, head-tossing, and hyperactivity. Additionally their coats are white with patches of normal-colored fur. The pathological changes in heterozygotes affect degeneration of the organ of Corti, stria vascularis, spiral ganglion, saccular macula, cristae ampullares, and vestibular ganglion. Viability of heterozygotes is nearly normal, but fertility is reduced. Mortality is very high in homozygotes, and very few of the survivors are fertile. Mice with the A419P missense mutation are known as Va mice; a second combination of mutations at molecular locations I362T and A419P, seen in the VaJ mouse has a less severe phenotype than the Va mouse
Amino acid change:  A419P
References:  4-5

References

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1. Castiglioni AJ, Remis NN, Flores EN, García-Añoveros J. (2011) Expression and vesicular localization of mouse Trpml3 in stria vascularis, hair cells, and vomeronasal and olfactory receptor neurons. J. Comp. Neurol., 519 (6): 1095-114. [PMID:21344404]

2. Cuajungco MP, Samie MA. (2008) The varitint-waddler mouse phenotypes and the TRPML3 ion channel mutation: cause and consequence. Pflugers Arch., 457 (2): 463-73. [PMID:18504603]

3. Curcio-Morelli C, Zhang P, Venugopal B, Charles FA, Browning MF, Cantiello HF, Slaugenhaupt SA. (2010) Functional multimerization of mucolipin channel proteins. J. Cell. Physiol., 222 (2): 328-35. [PMID:19885840]

4. Deol MS. (1954) The anomalies of the labyrinth of the mutants varitint-waddler, shaker-2 and jerker in the mouse. Journal of Genetics, 52: 558.

5. Di Palma F, Belyantseva IA, Kim HJ, Vogt TF, Kachar B, Noben-Trauth K. (2002) Mutations in Mcoln3 associated with deafness and pigmentation defects in varitint-waddler (Va) mice. Proc. Natl. Acad. Sci. U.S.A., 99 (23): 14994-9. [PMID:12403827]

6. Dong XP, Shen D, Wang X, Dawson T, Li X, Zhang Q, Cheng X, Zhang Y, Weisman LS, Delling M et al.. (2010) PI(3,5)P(2) controls membrane trafficking by direct activation of mucolipin Ca(2+) release channels in the endolysosome. Nat Commun, 1: 38. [PMID:20802798]

7. Grimm C. (2016) Endolysosomal Cation Channels as Therapeutic Targets—Pharmacology of TRPML Channels. Messenger, 5 (1/2): 30-36.

8. Grimm C, Cuajungco MP, van Aken AF, Schnee M, Jörs S, Kros CJ, Ricci AJ, Heller S. (2007) A helix-breaking mutation in TRPML3 leads to constitutive activity underlying deafness in the varitint-waddler mouse. Proc. Natl. Acad. Sci. U.S.A., 104 (49): 19583-8. [PMID:18048323]

9. Grimm C, Jörs S, Guo Z, Obukhov AG, Heller S. (2012) Constitutive activity of TRPML2 and TRPML3 channels versus activation by low extracellular sodium and small molecules. J. Biol. Chem., 287 (27): 22701-8. [PMID:22753890]

10. Grimm C, Jörs S, Saldanha SA, Obukhov AG, Pan B, Oshima K, Cuajungco MP, Chase P, Hodder P, Heller S. (2010) Small molecule activators of TRPML3. Chem. Biol., 17 (2): 135-48. [PMID:20189104]

11. Hirschi M, Herzik Jr MA, Wie J, Suo Y, Borschel WF, Ren D, Lander GC, Lee SY. (2017) Cryo-electron microscopy structure of the lysosomal calcium-permeable channel TRPML3. Nature, 550 (7676): 411-414. [PMID:29019979]

12. Kim HJ, Li Q, Tjon-Kon-Sang S, So I, Kiselyov K, Muallem S. (2007) Gain-of-function mutation in TRPML3 causes the mouse Varitint-Waddler phenotype. J. Biol. Chem., 282 (50): 36138-42. [PMID:17962195]

13. Kim HJ, Li Q, Tjon-Kon-Sang S, So I, Kiselyov K, Soyombo AA, Muallem S. (2008) A novel mode of TRPML3 regulation by extracytosolic pH absent in the varitint-waddler phenotype. EMBO J., 27 (8): 1197-205. [PMID:18369318]

14. Kim HJ, Soyombo AA, Tjon-Kon-Sang S, So I, Muallem S. (2009) The Ca(2+) channel TRPML3 regulates membrane trafficking and autophagy. Traffic, 10 (8): 1157-67. [PMID:19522758]

15. Martina JA, Lelouvier B, Puertollano R. (2009) The calcium channel mucolipin-3 is a novel regulator of trafficking along the endosomal pathway. Traffic, 10 (8): 1143-56. [PMID:19497048]

16. Nagata K, Zheng L, Madathany T, Castiglioni AJ, Bartles JR, García-Añoveros J. (2008) The varitint-waddler (Va) deafness mutation in TRPML3 generates constitutive, inward rectifying currents and causes cell degeneration. Proc. Natl. Acad. Sci. U.S.A., 105 (1): 353-8. [PMID:18162548]

17. Shen D, Wang X, Li X, Zhang X, Yao Z, Dibble S, Dong XP, Yu T, Lieberman AP, Showalter HD et al.. (2012) Lipid storage disorders block lysosomal trafficking by inhibiting a TRP channel and lysosomal calcium release. Nat Commun, 3: 731. [PMID:22415822]

18. Venkatachalam K, Hofmann T, Montell C. (2006) Lysosomal localization of TRPML3 depends on TRPML2 and the mucolipidosis-associated protein TRPML1. J. Biol. Chem., 281 (25): 17517-27. [PMID:16606612]

19. Venugopal B, Mesires NT, Kennedy JC, Curcio-Morelli C, Laplante JM, Dice JF, Slaugenhaupt SA. (2009) Chaperone-mediated autophagy is defective in mucolipidosis type IV. J. Cell. Physiol., 219 (2): 344-53. [PMID:19117012]

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21. Yamaguchi S, Jha A, Li Q, Soyombo AA, Dickinson GD, Churamani D, Brailoiu E, Patel S, Muallem S. (2011) Transient receptor potential mucolipin 1 (TRPML1) and two-pore channels are functionally independent organellar ion channels. J. Biol. Chem., 286 (26): 22934-42. [PMID:21540176]

22. Zeevi DA, Lev S, Frumkin A, Minke B, Bach G. (2010) Heteromultimeric TRPML channel assemblies play a crucial role in the regulation of cell viability models and starvation-induced autophagy. J. Cell. Sci., 123 (Pt 18): 3112-24. [PMID:20736310]

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How to cite this page

Haoxing Xu, David E. Clapham.
Transient Receptor Potential channels: TRPML3. Last modified on 01/02/2018. Accessed on 18/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=503.