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

Gamma-Protocadherins (PCDH-Gamma) regulate neuronal survival in the vertebrate central nervous system. The molecular mechanisms ofhow PCDH-Gamma mediates this function are still not understood. In this study, the authors show that through their common cytoplasmic domain, different PCDH-Gamma 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, the authors demonstrate that PDCD10 is required for the occurrence of apoptosis upon PCDH-Gamma depletion in developing chickenspinal neurons. Moreover, overexpression of PDCD10 is sufficient to induce neuronal apoptosis. Taken together, the authors' data reveal a novel function for PDCD10/CCM3, acting as a critical regulator of neuronal survival during development.