MTMR1, MTMR2, MTMR3, MTMR4, MTMR6, MTMR7, MTMR8 and Jumpy (also known as MTMR14), possess an active phosphatase domain, that specifically dephosphorylates 1-phosphatidyl-1D-myo-inositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate at position 3 on inositol ring
MTMR1, MTMR2, MTMR3, MTMR4, MTMR6, MTMR7, MTMR8 and Jumpy (also known as MTMR14), possess an active phosphatase domain, that specifically dephosphorylates 1-phosphatidyl-1D-myo-inositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate at position 3 on inositol ring
autophagy initiation is strictly dependent on phosphatidylinositol 3-phosphate synthesis. PI3P production is under tight control of PI3Kinase, hVps34, in complex with Beclin-1. PI3P metabolism involved in autophagy initiation is further regulated by the PI3P phosphatases Jumpy and MTMR3, and other PI3P phosphatases might be involved in this process
the enzyme plays central role in autophagy, overview. Regulation and cellular functions of PI3P phosphatases, protein interacting partners of active PI3P phosphatases, overview
PI3P is a substrate for PIP5-kinase, Fab1, also named PIKfyve, an enzyme that generates phosphoinositide 1-phosphatidyl-1D-myo-inositol 3,5-diphosphate
MTMR2-deficient mice develop CMT4B1-like neuropathy and azoospermia. MTMR13-deficient mice manifest myelin outfoldings in peripheral nerves. Jumpy or MTMR14-/- mice display muscle weakness and fatigue similar to patients with centronuclear myopathy
reduction of MTMR6 accelerates the transport of vesicular stomatitis virus glycoprotein in which Rab1B is involved. Furthermore, reduction of MTMR6 or Rab1B inhibits the formation of the tubular omegasome that is induced by overexpression of DFCP1 in autophagy
another animal model for Charcot-Marie-Tooth type 4B1 is produced by introducing the E276X mutation in exon 9. Phosphatase activity is inactivated toward PtdIns3P and PtdIns(3,5)P2. Nerve morphology in these mice is similar to that observed in Mtmr2-null mice, although a huge variability in the number of myelin outfoldings between different mice is noted. In both mutants, Mtmr2-null and E276X, the dysmyelinating phenotype is less severe than that observed in human Charcot-Marie-Tooth type 4B1
Mtmr2-null mouse are created as an animal model for Charcot-Marie-Tooth type 4B1 by removing exon 4, which encodes part of the PH-GRAM domain. Mice are viable. In both motor and sensory nerves of mutant mice, myelin outfoldings are observed starting at 3-4 weeks after birth. Semithin analysis is performed in longitudinal section of nerves. Myelin outfoldings predominantly arise at paranodal regions extending throughout the internode. At 12-15 months of age, myelin outfoldings also arise at Schmidt-Lanterman incisures, other regions enriched in Schwann cell cytoplasm. Axonal loss is observed only in Mtmr2-null mice at later stages (around 15 months) in more distal nerves. Dysmyelinating phenotype is less severe than that observed in human Charcot-Marie-Tooth type 4B1. Mtmr2-null mice have also defects in spermatogenesis, again, starting at 3-4 weeks of age
Mtmr2-null mouse are created as an animal model for Charcot-Marie-Tooth type 4B1 by removing exon 4, which encodes part of the PH-GRAM domain. Mice are viable. In both motor and sensory nerves of mutant mice, myelin outfoldings are observed starting at 3-4 weeks after birth. Semithin analysis is performed in longitudinal section of nerves. Myelin outfoldings predominantly arise at paranodal regions extending throughout the internode. At 12-15 months of age, myelin outfoldings also arise at Schmidt-Lanterman incisures, other regions enriched in Schwann cell cytoplasm. Axonal loss is observed only in Mtmr2-null mice at later stages (around 15 months) in more distal nerves. Dysmyelinating phenotype is less severe than that observed in human Charcot-Marie-Tooth type 4B1. Mtmr2-null mice have also defects in spermatogenesis, again, starting at 3-4 weeks of age
Mtm1 deficient mice have, after birth, normal muscle fibers with nuclei located at the periphery. Starting at 4 weeks of age, these mice develop a progressive myopathy characterized by hypotrophy and an increasing number of fibers with centrally located nuclei
Mtm1 deficient mice have, after birth, normal muscle fibers with nuclei located at the periphery. Starting at 4 weeks of age, these mice develop a progressive myopathy characterized by hypotrophy and an increasing number of fibers with centrally located nuclei
Mochizuki, Y.; Ohashi, R.; Kawamura, T.; Iwanari, H.; Kodama, T.; Naito, M.; Hamakubo, T.
Phosphatidylinositol 3-phosphatase myotubularin-related protein 6 (MTMR6) is regulated by small GTPase Rab1B in the early secretory and autophagic pathways