Dataset Information

PDCD10/CCM3 acts downstream of {gamma}-protocadherins to regulate neuronal survival.

ABSTRACT: ?-Protocadherins (PCDH-?) regulate neuronal survival in the vertebrate central nervous system. The molecular mechanisms of how PCDH-? mediates this function are still not understood. In this study, we show that through their common cytoplasmic domain, different PCDH-? 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-? 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.

SUBMITTER: Lin C

PROVIDER: S-EPMC3009895 | biostudies-other | 2010 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

PDCD10/CCM3 acts downstream of {gamma}-protocadherins to regulate neuronal survival.

Lin Chengyi C Meng Shuxia S Zhu Tina T Wang Xiaozhong X

The Journal of biological chemistry 20101101 53

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 ...[more]

PMID: 21041308

Similar Datasets

Project description:The yeast-to-hyphal morphotype transition and subsequent biofilm formation are important virulence factors of Candida albicans and are closely associated with ergosterol biosynthesis. Flo8 is an important transcription factor that determines filamentous growth and biofilm formation in C. albicans. However, the relationship between Flo8 and regulation of the ergosterol biosynthesis pathway remains elusive. Here, we analyzed the sterol composition of a flo8-deficient C. albicans strain by gas chromatography-mass spectrometry and observed the accumulation of the sterol intermediate zymosterol, the substrate of Erg6 (C-24 sterol methyltransferase). Accordingly, the transcription level of ERG6 was reduced in the flo8-deficient strain. Yeast one-hybrid experiments revealed that Flo8 physically interacted with the ERG6 promoter. Ectopic overexpression of ERG6 in the flo8-deficient strain partially restored biofilm formation and in vivo virulence in a Galleria mellonella infection model. These findings suggest that Erg6 is a downstream effector of the transcription factor Flo8 that mediates the cross talk between sterol synthesis and virulence factors in C. albicans. IMPORTANCE Biofilm formation by C. albicans hinders its eradication by immune cells and antifungal drugs. Flo8 is an important morphogenetic transcription factor that regulates the biofilm formation and in vivo virulence of C. albicans. However, little is known about how Flo8 regulates biofilm formation and fungal pathogenicity. Here, we determined that Flo8 directly binds to the promoter of ERG6 to positively regulate its transcriptional expression. Consistently, loss of flo8 results in the accumulation of the substrate of Erg6. Moreover, ectopic overexpression of ERG6 at least partially restores the biofilm formation and virulence of the flo8-deficient strain both in vitro and in vivo. This work provides a new perspective on the metabolic link between transcription factors and morphotypes in C. albicans.

Dataset Information

PDCD10/CCM3 acts downstream of {gamma}-protocadherins to regulate neuronal survival.

Publications

PDCD10/CCM3 acts downstream of {gamma}-protocadherins to regulate neuronal survival.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets