Vicky Yamamoto
Keck School of Medicine of USC
USA
Title: Protein phosphatase/Smek complex negatively regulate Par3 and promote neuronal differentiation.
Biography
Biography: Vicky Yamamoto
Abstract
Neural progenitor cells (NPCs) are self-renewing multipotent cells that are capable of differentiating into neurons and glial cells. Mechanisms that control the fate decisions of NPCs are not well understood. SMEK homolog 1, suppressor of mek1 (Smek-1) is a regulatory subunit of the serine/threonine protein phosphatase PP4. We found that Smek-1 is expressed in NPCs, promotes neuronal differentiation, and suppresses the proliferation of NPCs. Mass spectrometry analysis identified one of Smek-1’s binding partners, Par3. Par3, a cell polarity protein, is a negative regulator of neuronal differentiation. We demonstrate that Par3 is a substrate of Smek-1 and Smek-1 can negatively regulate its activity in neurogenesis. Interestingly, Smek-1 is expressed mainly in the nucleus but is exclusively localized in the cytoplasm during mitosis. We show that the cytoplasmic Smek-1 can interact with cytoplasmic Par3 and thereby mediate de-phosphorylation by the catalytic subunit PP4C. Collectively, our results show that the PP4/Smek-1 complex is likely a key regulator of neurogenesis.
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