PDCD10/CCM3 acts downstream of {gamma}-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 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.
Department of Molecular Biosciences, Northwestern University, Evanston, Illinois 60208, USA.
Chengyi
C
Lin
Shuxia
S
Meng
Tina
T
Zhu
Xiaozhong
X
Wang
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000502:physiology*; D000070585:Cadherin Related Proteins; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D002645:Chickens; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D025941:Protein Interaction Mapping; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D034622:RNA Interference; D015398:Signal Transduction
D051017:Apoptosis Regulatory Proteins; D000070585:Cadherin Related Proteins; D015820:Cadherins; C464785:Gamma-protocadherins; D008565:Membrane Proteins; C495390:PDCD10 protein, human; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins