Leading tip drives soma translocation via forward F-actin flow during neuronal migration.
Neuronal migration involves coordinated extension of the leading process and translocation of the soma, but the relative contribution of different subcellular regions, including the leading process and cell rear, in driving soma translocation remains unclear. By local manipulation of cytoskeletal components in restricted regions of cultured neurons, we examined the molecular machinery underlying the generation of traction force for soma translocation during neuronal migration. In actively migrating cerebellar granule cells in culture, a growth cone (GC)-like structure at the leading tip exhibits high dynamics, and severing the tip or disrupting its dynamics suppressed soma translocation within minutes. Soma translocation was also suppressed by local disruption of F-actin along the leading process but not at the soma, whereas disrupting microtubules along the leading process or at the soma accelerated soma translocation. Fluorescent speckle microscopy using GFP-alpha-actinin showed that a forward F-actin flow along the leading process correlated with and was required for soma translocation, and such F-actin flow depended on myosin II activity. In migrating neurons, myosin II activity was high at the leading tip but low at the soma, and increasing or decreasing this front-to-rear difference accelerated or impeded soma advance. Thus, the tip of the leading process actively pulls the soma forward during neuronal migration through a myosin II-dependent forward F-actin flow along the leading process.
He
Min
M
Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Zhang
Zheng-hong
ZH
Guan
Chen-bing
CB
Xia
Di
D
Yuan
Xiao-bing
XB
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D003208:Concanavalin A / Q000494:pharmacology; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics; D020439:Growth Cones / Q000502:physiology*; D018613:Microscopy, Confocal / Q000379:methods; D008870:Microtubules / Q000378:metabolism; D008934:Mitogens / Q000494:pharmacology; D018994:Myosin Light Chains / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D015739:Nocodazole / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D053778:Thiazolidines / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection / Q000379:methods; D050257:Tubulin Modulators / Q000494:pharmacology
D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D008934:Mitogens; D018994:Myosin Light Chains; D053778:Thiazolidines; D050257:Tubulin Modulators; D003208:Concanavalin A; D049452:Green Fluorescent Proteins; D015739:Nocodazole; C037067:latrunculin A