| 2001 |
MTMR3 is an inositol lipid 3-phosphatase that hydrolyzes both PtdIns3P and PtdIns(3,5)P2 in vitro and in S. cerevisiae, and provides the first defined cellular route for production of PtdIns5P. Overexpression of catalytically dead MTMR3 (C413S) in mammalian cells induces striking vacuolar compartments enriched in mutant protein. |
In vitro phosphatase assay, heterologous expression in S. cerevisiae, active-site mutagenesis (C413S), overexpression in mammalian cells |
Current biology : CB |
High |
11676921
|
| 2000 |
FYVE-DSP1 (MTMR3) is a dual-specificity phosphatase containing a C-terminal FYVE domain; recombinant protein partitions in both cytosolic and membrane fractions, dephosphorylates proteins phosphorylated on Ser, Thr, and Tyr residues, and is inactivated by mutation of the catalytic cysteinyl residue. Three isoforms from alternate RNA splicing are expressed. |
Molecular cloning, subcellular fractionation, in vitro phosphatase assay with phosphoprotein and pNPP substrates, active-site mutagenesis, inhibitor characterization (sodium vanadate/pervanadate), RT-PCR tissue distribution |
Biochemical and biophysical research communications |
Medium |
10733931
|
| 2005 |
The FYVE domain of MTMR3 is atypical: it neither confers endosomal localization nor binds PtdIns3P, and is not required for in vitro phosphatase activity. In contrast, the N-terminal PH-GRAM domain binds phosphoinositides with preference for PtdIns5P as an allosteric regulator, is required for in vitro activity, and mediates plasma-membrane translocation in response to ectopically produced PtdIns5P. Combined PH-GRAM deletion with an active-site mutation localizes MTMR3 to the Golgi complex. |
Lipid-binding assays, in vitro phosphatase assay with deletion/point mutants, ectopic expression of bacterial phosphatase IpgD, live-cell fluorescence microscopy |
Journal of cell science |
High |
15840652
|
| 2010 |
MTMR3 negatively regulates autophagosome formation and size by locally depleting PtdIns3P at autophagosome formation sites. Overexpression of phosphatase-dead MTMR3 partially localizes to autophagosomes and causes accumulation of PtdIns3P and PtdIns3P-binding proteins DFCP1 and WIPI-1α there. Knockdown of MTMR3 increases autophagosome formation; wild-type MTMR3 overexpression reduces autophagosome size and overall autophagic activity. |
Dominant-negative overexpression, siRNA knockdown, fluorescence microscopy (GFP-DFCP1, GFP-WIPI-1α reporters), autophagosome quantification |
Traffic (Copenhagen, Denmark) |
High |
20059746
|
| 2012 |
MTMR3, together with the lipid kinase PIKfyve, constitutes a phosphoinositide loop that produces PtdIns5P via PtdIns(3,5)P2, and this PtdIns5P production promotes cell migration. Class III PI3K activity was upstream, and depletion of MTMR3 (or PIKfyve) decreased fibroblast migration; exogenous PtdIns5P or a PtdIns5P-producing bacterial enzyme directly stimulated migration. |
siRNA knockdown, cell migration screen, exogenous lipid supplementation, bacterial enzyme expression, Drosophila in vivo migration model |
EMBO reports |
High |
23154468
|
| 2014 |
PIKfyve and MTMR3 regulate cancer cell migration and invasion through activation of the Rho-family GTPase Rac1. Depletion of MTMR3 or inhibition of PIKfyve enzymatic activity reduces cell velocity in multiple cancer cell lines, and PtdIns5P is implicated in Rac1 activation downstream of these enzymes. |
siRNA knockdown, enzymatic inhibitor (YM201636), cell tracking software, Rac1 activation assay, invasion assay |
The Biochemical journal |
Medium |
24840251
|
| 2015 |
MTMR3 decreases PRR-induced PtdIns3P and autophagy levels in human macrophages, thereby increasing caspase-1 activation, autocrine IL-1β secretion, and NF-κB signaling. This regulation requires the N-terminal PH-GRAM domain and the catalytic Cys413 residue. In MTMR3-deficient macrophages, reducing enhanced autophagy or restoring NF-κB signaling rescues PRR-induced cytokines. |
siRNA knockdown, domain-deletion and point mutants (Cys413), PtdIns3P measurement, autophagy assays, caspase-1 activation assay, NF-κB signaling assays, cytokine secretion measurements, epistasis with autophagy inhibitors |
Proceedings of the National Academy of Sciences of the United States of America |
High |
26240347
|
| 2015 |
MTMR3 physically interacts with mTORC1 and suppresses its kinase activity. The N-terminal half of MTMR3 (containing PH-G and phosphatase domains) is necessary and sufficient for mTORC1 binding and suppression. Phosphatase-deficient MTMR3 provides more robust mTORC1 suppression than wild-type and, together with the phosphatase domain alone, localizes to the Golgi. |
Co-immunoprecipitation, overexpression of wild-type and phosphatase-dead MTMR3 constructs, domain-deletion analysis, mTORC1 activity assays (S6K phosphorylation), fluorescence microscopy |
FEBS letters |
Medium |
26787466
|
| 2019 |
MTMR3 and MTMR4 together regulate STING trafficking and innate immune responses to cytoplasmic DNA. Double knockout (DKO) of MTMR3/MTMR4 in macrophages enhanced type I interferon production and IRF3 phosphorylation after ISD stimulation and HSV-1 infection, caused rapid STING translocation from ER to Golgi, and led to STING accumulation in enlarged PtdIns3P-positive cytosolic puncta, consistent with MTMR3/4 dephosphorylating PtdIns3P to control these compartments. |
CRISPR/Cas9 double knockout, ISD stimulation and HSV-1 infection, type I IFN and IRF3 phosphorylation measurement, fluorescence microscopy for STING/PtdIns3P colocalization |
The Journal of biological chemistry |
Medium |
30944173
|
| 2023 |
MTMR3 enhances Toll-like receptor 9-induced IgA production in a manner dependent on its phosphatidylinositol 3-phosphate binding domain. Mtmr3-knockout mice show defective TLR9-induced IgA production, reduced glomerular IgA deposition, and reduced mesangial cell proliferation; RNA-seq revealed an impaired intestinal immune network for IgA production in KO animals. |
Mtmr3 knockout mice, TLR9 stimulation, serum IgA measurement, glomerular IgA deposition histology, domain-binding mutant in vitro studies, RNA-seq pathway analysis |
Kidney international |
Medium |
37414396
|