Discs large 5 is required for polarization of citron kinase in mitotic neural precursors.
Citron kinase (CitK), a protein essential to neurogenic cell division in the central nervous system, is highly polarized in neural progenitors. The mechanisms that polarize CitK to cellular domains that line the ventricular surface of neuroepithelium are currently not known. Here we report that Discs large 5 (Dlg5), a member of the MAGUK family, is an interactor of CitK required for CitK polarization. The CitK-Dlg5 interaction was first revealed in a protein array screen of proteins containing PDZ domains, and then subsequently confirmed by co-immunoprecipitation. Moreover, in Dlg5 (-/-) mice CitK fails to polarize in mitotic neuronal precursors. In addition, the total number of mitotic progenitors and the ratio of ventricular to abventricular mitotic progenitors in developing neocortex are significantly decreased in Dlg5 (-/-) embryos. Dlg5 is therefore required to maintain the polarization of a protein essential to neurogenic cytokinesis, and plays a role in localizing cell divisions to the surface of the lateral ventricles in embryonic brain.
Chang
Yoonjeung
Y
1Department of Physiology and Neurobiology, University of Connecticut, Storrs, CT USA.
Klezovitch
Olga
O
Walikonis
Randall S
RS
Vasioukhin
Valera
V
LoTurco
Joseph J
JJ
D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D020547:Lateral Ventricles / Q000196:embryology / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D051381:Rats
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C115635:citron-kinase; D017346:Protein Serine-Threonine Kinases; C523873:Dlg5 protein, mouse; D051528:Guanylate Kinases