Involvement of filamin A and filamin A-interacting protein (FILIP) in controlling the start and cell shape of radially migrating cortical neurons.
Precisely regulated radial cell migration out of the ventricular zone is essential for corticogenesis. However, molecular mechanisms controlling the start of migration and the dynamics of migrating cell shape remain elusive. Here, we show novel mechanisms that can tether ventricular zone cells and control migrating cell shape. The novel protein Filamin A-interacting protein (FILIP) interacts with Filamin A, an indispensable actin-binding protein for cell motility, and induces its degradation in COS-7 cells. Degradation of Filamin A is indicated in the cortical ventricular zone where FILIP mRNA localizes. Furthermore, most ventricular zone cells that overexpress FILIP fail to migrate in explants. These results indicate that FILIP acts through a Filamin A-F-actin axis to control the start of neocortical cell migration from the ventricular zone. Filamin A also determines the shape of migrating neocortical neurons, which show global morphological changes and complicated behavior during that migration. Dysfunction of Filamin A, caused by a mutant Filamin A expression, prevents cells from acquiring consistent polarity toward specific direction and decreases motility in the subventricular and intermediate zones. In contrast, Filamin A overexpression, achieved by a short interfering RNA for FILIP, promotes the development and maintenance of a bipolar shape also in the subventricular and intermediate zones. These results suggest that the amount of Filamin A helps migrating neurons determine their mode of migration, multipolar or bipolar, prior to entering the cortical plate and that FILIP is responsible, at least in part, for the Filamin A content of migrating neurons.
Sato
Makoto
M
Division of Cell Biology and Neuroscience, Department of Morphological and Physiological Sciences, Faculty of Medical Sciences, University of Fukui, Matsuoka, Fukui, Japan. makosato@fmsrsa.fukui-med.ac.jp
Nagano
Takashi
T
D000818:Animals; D019556:COS Cells / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology; D048430:Cell Shape / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology* / Q000196:embryology; D002522:Chlorocebus aethiops; D003285:Contractile Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D064448:Filamins; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D038081:Organogenesis
D002352:Carrier Proteins; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; C464562:FILIP1 protein, human; D064448:Filamins; D008840:Microfilament Proteins