PDCD10/CCM3 Acts Downstream of γ-Protocadherins to Regulate Neuronal Survival

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 intra...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of biological chemistry 2010-12, Vol.285 (53), p.41675-41685
Main Authors: Lin, Chengyi, Meng, Shuxia, Zhu, Tina, Wang, Xiaozhong
Format: Article
Language:English
Subjects:
Apoptosis
Cell Adhesion
Cell Death
Neurobiology
Neurodevelopment
Protein-Protein Interactions
Signal Transduction
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M110.179895