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Publication : CLASP2 Links Reelin to the Cytoskeleton during Neocortical Development.

First Author  Dillon GM Year  2017
Journal  Neuron Volume  93
Issue  6 Pages  1344-1358.e5
PubMed ID  28285824 Mgi Jnum  J:269775
Mgi Id  MGI:6269149 Doi  10.1016/j.neuron.2017.02.039
Citation  Dillon GM, et al. (2017) CLASP2 Links Reelin to the Cytoskeleton during Neocortical Development. Neuron 93(6):1344-1358.e5
abstractText  The Reelin signaling pathway plays a crucial role in regulating neocortical development. However, little is known about how Reelin controls the cytoskeleton during neuronal migration. Here, we identify CLASP2 as a key cytoskeletal effector in the Reelin signaling pathway. We demonstrate that CLASP2 has distinct roles during neocortical development regulating neuron production and controlling neuron migration, polarity, and morphogenesis. We found downregulation of CLASP2 in migrating neurons leads to mislocalized cells in deeper cortical layers, abnormal positioning of the centrosome-Golgi complex, and aberrant length/orientation of the leading process. We discovered that Reelin regulates several phosphorylation sites within the positively charged serine/arginine-rich region that constitute consensus GSK3beta phosphorylation motifs of CLASP2. Furthermore, phosphorylation of CLASP2 regulates its interaction with the Reelin adaptor Dab1 and this association is required for CLASP2 effects on neurite extension and motility. Together, our data reveal that CLASP2 is an essential Reelin effector orchestrating cytoskeleton dynamics during brain development.
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