Myosin II has distinct functions in PNS and CNS myelin sheath formation.
The myelin sheath forms by the spiral wrapping of a glial membrane around the axon. The mechanisms responsible for this process are unknown but are likely to involve coordinated changes in the glial cell cytoskeleton. We have found that inhibition of myosin II, a key regulator of actin cytoskeleton dynamics, has remarkably opposite effects on myelin formation by Schwann cells (SC) and oligodendrocytes (OL). Myosin II is necessary for initial interactions between SC and axons, and its inhibition or down-regulation impairs their ability to segregate axons and elongate along them, preventing the formation of a 1:1 relationship, which is critical for peripheral nervous system myelination. In contrast, OL branching, differentiation, and myelin formation are potentiated by inhibition of myosin II. Thus, by controlling the spatial and localized activation of actin polymerization, myosin II regulates SC polarization and OL branching, and by extension their ability to form myelin. Our data indicate that the mechanisms regulating myelination in the peripheral and central nervous systems are distinct.
Wang
Haibo
H
Department of Biological Sciences, Hunter College, City University of New York, New York, NY 10065, USA.
Tewari
Ambika
A
Einheber
Steven
S
Salzer
James L
JL
Melendez-Vasquez
Carmen V
CV
D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism*; D018920:Coculture Techniques; D003599:Cytoskeleton / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D024462:Myosin Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D017933:Peripheral Nervous System / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism
D000199:Actins; D015415:Biomarkers; D015820:Cadherins; D006576:Heterocyclic Compounds, 4 or More Rings; D004676:Myelin Basic Protein; C472645:blebbistatin; D024462:Myosin Type II
Ann N Y Acad Sci. 1986;486:241-7
3471156
Neuron. 2004 Jul 22;43(2):183-91
15260955
Mol Cell Neurosci. 2001 Apr;17(4):624-36
11312599
J Neurosci. 2004 Aug 11;24(32):7140-9
15306647
Science. 2003 Mar 14;299(5613):1743-7
12637748
J Neurosci. 2006 Mar 29;26(13):3390-5
16571745
Curr Opin Cell Biol. 1999 Feb;11(1):26-33
10047526
J Cell Biol. 1989 Jul;109(1):273-84
2745552
Nat Cell Biol. 2007 Oct;9(10):1110-21
17909522
Glia. 2008 Feb;56(3):284-93
18080294
Nat Cell Biol. 2006 Mar;8(3):215-26
16501565
Mol Biol Cell. 2007 Jun;18(6):2305-12
17429076
Mol Biol Cell. 2005 Oct;16(10):4531-42
16030252
Neuron. 2003 Oct 9;40(2):297-318
14556710
Glia. 2007 Jun;55(8):844-58
17405146
Curr Biol. 2005 Apr 26;15(8):732-6
15854905
Cell Tissue Res. 1986;244(1):27-38
3516402
J Neurobiol. 2006 Jul;66(8):847-67
16673385
J Neurosci. 2007 Oct 17;27(42):11366-75
17942731
J Biol Chem. 2004 Jan 23;279(4):2800-8
14594953
Methods. 2001 Aug;24(4):331-9
11465998
J Neurosci. 2002 May 15;22(10):4066-79
12019326
J Cell Biol. 2007 Jun 18;177(6):1051-61
17576798
J Neurosci. 2006 Oct 4;26(40):10110-9
17021167
Nat Genet. 2003 Mar;33(3):401-6
12590264
J Neurosci. 2008 Jan 2;28(1):264-78
18171944
Neuron. 2005 Sep 1;47(5):681-94
16129398
Curr Opin Cell Biol. 2006 Feb;18(1):26-31
16337782
J Neurosci. 2006 Nov 22;26(47):12174-85
17122042
Nat Rev Neurosci. 2005 Sep;6(9):671-82
16136171
Science. 2006 Nov 3;314(5800):832-6
17082460
Nat Rev Neurosci. 2006 Jan;7(1):11-8
16371946
J Cell Biol. 1995 Apr;129(2):443-58
7536747
J Neuropathol Exp Neurol. 2007 Jul;66(7):608-16
17620986
Exp Cell Res. 2006 May 15;312(9):1637-50
16519885
J Cell Biol. 2004 Feb 2;164(3):427-39
14757754
Neuron. 2002 Dec 5;36(5):855-68
12467589
Glia. 2006 Apr 1;53(5):563-6
16355369
J Cell Sci. 2008 Jan 1;121(Pt 1):11-8
18096687
J Cell Biol. 2000 Aug 21;150(4):797-806
10953004
Mol Biol Cell. 2005 Jun;16(6):2636-50
15800060
J Neurosci. 2004 Apr 21;24(16):3953-63
15102911
J Neurosci. 2007 Mar 28;27(13):3560-70
17392472
Nat Cell Biol. 2007 Mar;9(3):299-309
17310241
J Cell Biol. 2007 Jun 18;177(6):1063-75
17576799
J Neurobiol. 2001 Oct;49(1):62-78
11536198
Mol Biol Cell. 2004 Mar;15(3):982-9
14699073
J Mol Biol. 2008 Jan 11;375(2):325-30
18021803
J Neurosci. 1998 Nov 15;18(22):9303-11
9801369
J Neurosci. 2006 May 24;26(21):5849-59
16723544
Trends Cell Biol. 1993 Jun;3(6):191-7
14731493
J Neurosci. 1997 Jan 1;17(1):241-50
8987752
J Neurosci. 2007 Jun 6;27(23):6185-96
17553990