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Details

Autor(en) / Beteiligte
Titel
ADF/Cofilin-Mediated Actin Retrograde Flow Directs Neurite Formation in the Developing Brain
Ist Teil von
  • Neuron (Cambridge, Mass.), 2012-12, Vol.76 (6), p.1091-1107
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2012
Quelle
MEDLINE
Beschreibungen/Notizen
  • Neurites are the characteristic structural element of neurons that will initiate brain connectivity and elaborate information. Early in development, neurons are spherical cells but this symmetry is broken through the initial formation of neurites. This fundamental step is thought to rely on actin and microtubule dynamics. However, it is unclear which aspects of the complex actin behavior control neuritogenesis and which molecular mechanisms are involved. Here, we demonstrate that augmented actin retrograde flow and protrusion dynamics facilitate neurite formation. Our data indicate that a single family of actin regulatory proteins, ADF/Cofilin, provides the required control of actin retrograde flow and dynamics to form neurites. In particular, the F-actin severing activity of ADF/Cofilin organizes space for the protrusion and bundling of microtubules, the backbone of neurites. Our data reveal how ADF/Cofilin organizes the cytoskeleton to drive actin retrograde flow and thus break the spherical shape of neurons. ► Actin retrograde flow and dynamics direct neurite growth out of the neuronal sphere ► ADF/Cofilin is a key regulator of neuritogenesis during brain development ► ADF/Cofilin drives actin retrograde flow and dynamics ► ADF/Cofilin activity enables the growth of bundled microtubules to form neurites Flynn et al. show that ADF/Cofilin regulates the actin turnover dynamics necessary for neurite formation in the developing brain. This work challenges the wide-held view that retrograde flow is primarily driven by the action of actin polymerization and myosin II.

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