PDCD10/CCM3 acts downstream of {gamma}-protocadherins to regulate neuronal survival |
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Authors: | Lin Chengyi Meng Shuxia Zhu Tina Wang Xiaozhong |
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Institution: | Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA. |
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Abstract: | γ-Protocadherins (PCDH-γ) regulate neuronal survival in the vertebrate central nervous system. The molecular mechanisms of how PCDH-γ mediates this function are still not understood. In this study, we show that through their common cytoplasmic domain, different PCDH-γ isoforms interact with an intracellular adaptor protein named PDCD10 (programmed cell death 10). PDCD10 is also known as CCM3, a causative genetic defect for cerebral cavernous malformations in humans. Using RNAi-mediated knockdown, we demonstrate that PDCD10 is required for the occurrence of apoptosis upon PCDH-γ depletion in developing chicken spinal neurons. Moreover, overexpression of PDCD10 is sufficient to induce neuronal apoptosis. Taken together, our data reveal a novel function for PDCD10/CCM3, acting as a critical regulator of neuronal survival during development. |
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Keywords: | Apoptosis Cell Adhesion Cell Death Neurodevelopment Protein-Protein Interactions Signal Transduction |
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