Dysregulation of myelin synthesis and actomyosin function underlies aberrant myelin in CMT4B1 neuropathy
Copyright policy )Dysregulation of myelin synthesis and actomyosin function underlies aberrant myelin in CMT4B1 neuropathy
SignificanceCharcot-Marie-Tooth type 4B1 (CMT4B1) is a very severe demyelinating neuropathy with childhood onset, characterized by myelin outfoldings, a pathological aberrant form of myelination. This morphology may be the consequence of an excessive longitudinal growth of the myelinated internode during postnatal nerve development. We first demonstrated that loss of MTMR2 (Myotubularin-related 2) phosphatase causes CMT4B1. MTMR2 dephosphorylates phospholipids, important regulators of membrane trafficking, which is a key process in Schwann cells, the myelinating cells in the PNS. However, why loss of MTMR2 provokes CMT4B1 remains to be assessed. Here we propose a mechanism by which MTMR2, by regulating PtdIns(3,5)P2phosphoinositide levels, coordinates myelin synthesis and RhoA/myosin II-dependent cytoskeletal dynamics necessary to expand the membrane and promote myelin growth.
Charcot-Marie-Tooth neuropathies; Schwann cells; myelin; myotubularin; phosphoinositides; Animals; Charcot-Marie-Tooth Disease; Mechanistic Target of Rapamycin Complex 1; Mice; Mice, Knockout; Myelin Sheath; Myosin Type II; Phosphatidylinositol Phosphates; Protein Tyrosine Phosphatases, Non-Receptor; rhoA GTP-Binding Protein; Signal Transduction, Mice, Knockout, Myosin Type II, phosphoinositides, Mechanistic Target of Rapamycin Complex 1, Protein Tyrosine Phosphatases, Non-Receptor, myotubularin, Charcot-Marie-Tooth neuropathies, myelin, Mice, Phosphatidylinositol Phosphates, Charcot-Marie-Tooth Disease, Animals, Schwann cells, rhoA GTP-Binding Protein, Myelin Sheath, Signal Transduction
Charcot-Marie-Tooth neuropathies; Schwann cells; myelin; myotubularin; phosphoinositides; Animals; Charcot-Marie-Tooth Disease; Mechanistic Target of Rapamycin Complex 1; Mice; Mice, Knockout; Myelin Sheath; Myosin Type II; Phosphatidylinositol Phosphates; Protein Tyrosine Phosphatases, Non-Receptor; rhoA GTP-Binding Protein; Signal Transduction, Mice, Knockout, Myosin Type II, phosphoinositides, Mechanistic Target of Rapamycin Complex 1, Protein Tyrosine Phosphatases, Non-Receptor, myotubularin, Charcot-Marie-Tooth neuropathies, myelin, Mice, Phosphatidylinositol Phosphates, Charcot-Marie-Tooth Disease, Animals, Schwann cells, rhoA GTP-Binding Protein, Myelin Sheath, Signal Transduction
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