RanBPM regulates the progression of neuronal precursors through M-phase at the surface of the neocortical ventricular zone.
Many of the mitoses that produce pyramidal neurons in neocortex occur at the dorsolateral surface of the lateral ventricles in the embryo. RanBPM was found in a yeast two-hybrid screen to potentially interact with citron kinase (CITK), a protein shown previously to localize to the surface of the lateral ventricles and to be essential to neurogenic mitoses. Similar to its localization in epithelia, RanBPM protein is concentrated at the adherens junctions in developing neocortex. The biochemical interaction between CITK and RanBPM was confirmed in coimmunoprecipitation and protein overlay experiments. To test for a functional role of RanPBM in vivo, we used in utero RNAi. RanBPM RNAi decreased the polarization of CITK to the ventricular surface, increased the number of cells in mitosis, and decreased the number of cells in cytokinesis. Finally, the effect of RanBPM knockdown on mitosis was reversed in embryos mutant for CITK. Together, these results indicate that RanBPM, potentially through interaction with CITK, plays a role in the progression of neocortical precursors through M-phase at the ventricular surface.
Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut, USA.
Yoonjeung
Y
Chang
Murugan
M
Paramasivam
Matthew J
MJ
Girgenti
Randall S
RS
Walikonis
Elisabetta
E
Bianchi
Joseph J
JJ
LoTurco
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D022005:Adherens Junctions / Q000502:physiology; D000818:Animals; D002455:Cell Division / Q000502:physiology*; D002462:Cell Membrane / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D002552:Cerebral Ventricles / Q000196:embryology / Q000502:physiology; D048749:Cytokinesis / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D019579:Neocortex / Q000196:embryology / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D017208:Rats, Wistar; D055153:Stem Cell Niche / Q000502:physiology*; D013234:Stem Cells / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; C116005:Ran binding protein 9; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases