Myosin Va controls oligodendrocyte morphogenesis and myelination.
A product of myosin Va mutations, Griscelli's syndrome type 1 (GS1) is characterized by several neurologic deficits including quadraparesis, mental retardation, and seizures. Although multiple studies have not clearly established a cause for the neurologic deficits linked with GS1, a few reports suggest that GS1 is associated with abnormal myelination, which could cause the neurologic deficits seen with GS1. In this report, we investigate whether myosin Va is critical to oligodendrocyte morphology and to myelination in vivo. We found that myosin Va-null mice exhibit significantly impaired myelination of the brain, optic nerve, and spinal cord. Oligodendrocytes express myosin Va and loss of myosin Va function resulted in significantly smaller lamellas and decreased process number, length, and branching of oligodendrocytes. Loss of myosin Va function also blocked distal localization of vesicle-associated membrane protein 2 (VAMP2), which is known to associate with myosin Va. When VAMP2 function was disrupted, oligodendrocytes exhibited similar morphologic deficits to what is seen with functional ablation of myosin Va. Our findings establish a role for both myosin Va and VAMP2 in oligodendrocyte function as it relates to myelination.
Sloane
Jacob A
JA
Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine, Boston, Massachusetts 02215, USA.
Vartanian
Timothy K
TK
D000818:Animals; D001921:Brain / Q000166:cytology / Q000254:growth & development; D002478:Cells, Cultured; D051379:Mice; D018345:Mice, Knockout; D009024:Morphogenesis / Q000235:genetics / Q000502:physiology*; D009186:Myelin Sheath / Q000378:metabolism / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D024701:Myosin Type V / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050988:Vesicle-Associated Membrane Protein 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology
C513082:Myo5a protein, mouse; D050988:Vesicle-Associated Membrane Protein 2; D024701:Myosin Type V; D018995:Myosin Heavy Chains