title: Protein phosphatase 4 and Smek complex negatively regulate Par3 and promote neuronal differentiation of neural stem/progenitor cells.
abstract: Neural progenitor cells (NPCs) are multipotent cells that can self-renew and differentiate into neurons and glial cells. However, mechanisms that control their fate decisions are poorly understood. Here, we show that Smek1, a regulatory subunit of the serine/threonine protein phosphatase PP4, promotes neuronal differentiation and suppresses the proliferative capacity of NPCs. We identify the cell polarity protein Par3, a negative regulator of neuronal differentiation, as a Smek1 substrate and demonstrate that Smek1 suppresses its activity. We also show that Smek1, which is predominantly nuclear in NPCs, is excluded from the nucleus during mitosis, allowing it to interact with cortical/cytoplasmic Par3 and mediate its dephosphorylation by the catalytic subunit PP4c. These results identify the PP4/Smek1 complex as a key regulator of neurogenesis.
authors.affiliation: Catholic Institute for Visual Science, Department of Ophthalmology and Visual Science, College of Medicine, The Catholic University of Korea, Seoul 137-040, South Korea; The Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90042, USA. Electronic address: jmlyu@catholic.ac.kr.
authors.forename: Jungmook
authors.initials: J
authors.lastname: Lyu
authors.forename: Hee-Ryang
authors.initials: HR
authors.lastname: Kim
authors.forename: Vicky
authors.initials: V
authors.lastname: Yamamoto
authors.forename: Si Ho
authors.initials: SH
authors.lastname: Choi
authors.forename: Zong
authors.initials: Z
authors.lastname: Wei
authors.forename: Choun-Ki
authors.initials: CK
authors.lastname: Joo
authors.forename: Wange
authors.initials: W
authors.lastname: Lu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D058953:Neural Stem Cells / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D010749:Phosphoprotein Phosphatases / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D016548:Prosencephalon / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; C115084:Pard3 protein, mouse; D010749:Phosphoprotein Phosphatases; C561096:Ppp4r3a protein, mouse; C080406:protein phosphatase 4