4.7 Article

Differential roles of α-, β-, and γ-actin in axon growth and collateral branch formation in motoneurons

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JOURNAL OF CELL BIOLOGY
卷 216, 期 3, 页码 793-814

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ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201604117

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资金

  1. Deutsche Forschungsgemeinschaft [SPP 1738, SE697/5-1]
  2. Hermann-and-Lilli Schilling Stiftung
  3. Bavarian excellence program ForIPS [D2-F2412, 26]
  4. Bundesministerium fur Bildung und Forschung Dystract [TP6]
  5. European Community [259867]

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Axonal branching and terminal arborization are fundamental events during the establishment of synaptic connectivity. They are triggered by assembly of actin filaments along axon shafts giving rise to filopodia. The specific contribution of the three actin isoforms, Act alpha, Act beta, and Act gamma, to filopodia stability and dynamics during this process is not well understood. Here, we report that Act alpha, Act beta, and Act gamma isoforms are expressed in primary mouse motoneurons and their transcripts are translocated into axons. shRNA-mediated depletion of Act alpha reduces axonal filopodia dynamics and disturbs collateral branch formation. Knockdown of Act beta reduces dynamic movements of growth cone filopodia and impairs presynaptic differentiation. Ablation of Act beta or Act gamma leads to compensatory up-regulation of the two other isoforms, which allows maintenance of total actin levels and preserves F-actin polymerization. Collectively, our data provide evidence for specific roles of different actin isoforms in spatial regulation of actin dynamics and stability in axons of developing motoneurons.

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