Myosin IIB is required for growth cone motility.
Growth cones are required for the forward advancement and navigation of growing axons. Modulation of growth cone shape and reorientation of the neurite are responsible for the change of outgrowth direction that underlies navigation. Change of shape involves the reordering of the cytoskeleton. Reorientation of the neurite requires the generation of tension, which is supplied by the ability of the growth cone to crawl on a substrate. The specific molecular mechanisms responsible for these activities are unknown but are thought to involve actomyosin-generated force combined with linkage to the cell surface receptors that are responsible for adhesion (Heidemann and Buxbaum, 1998). To test whether myosin IIB is responsible for the force generation, we quantified shape dynamics and filopodial-mediated traction force in growth cones from myosin IIB knock-out (KO) mice and compared them with neurons from normal littermates. Growth cones from the KO mice spread less, showed alterations in shape dynamics and actin organization, and had reduced filopodial-mediated traction force. Although peak traction forces produced by filopodia of KO cones were decreased significantly, KO filopodia occasionally developed forces equivalent to those in the wild type. This indicates that other myosins participate in filopodial-dependent traction force. Therefore, myosin IIB is necessary for normal growth cone spreading and the modulation of shape and traction force but acts in combination with other myosins for some or all of these activities. These activities are essential for growth cone forward advancement, which is necessary for outgrowth. Thus outgrowth is slowed, but not eliminated, in neurons from the myosin IIB KO mice.
Bridgman
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Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. bridgmap@pcg.wustl.edu
Dave
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Asnes
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Tullio
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Adelstein
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D000180:Acrylic Resins / Q000378:metabolism / Q000494:pharmacology; D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002478:Cells, Cultured; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D018345:Mice, Knockout; D008856:Microscopy, Fluorescence; D008863:Microspheres; D018995:Myosin Heavy Chains / Q000172:deficiency / Q000235:genetics; D009218:Myosins / Q000378:metabolism* / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D024501:Nonmuscle Myosin Type IIB; D010641:Phenotype; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D013314:Stress, Mechanical; D017783:Superior Cervical Ganglion; D013997:Time Factors
D000180:Acrylic Resins; D000199:Actins; C016680:polyacrylamide gels; D024501:Nonmuscle Myosin Type IIB; C103815:nonmuscle myosin type IIB heavy chain; D018995:Myosin Heavy Chains; D009218:Myosins