Gamma-1-Syntrophin Mediates Trafficking of Gamma-Enolase towards the Plasma Membrane and Enhances Its Neurotrophic Activity

Neuro-signals

关键词: Gamma-1-syntrophin;    Gamma-enolase;    Cathepsin X;    Intracellular trafficking;    Neurotrophic effect;   

DOI  :  10.1159/000324292

学科分类：神经科学

来源: S Karger AG

【 摘 要 】

Syntrophins are scaffold proteins that can bind several signaling molecules and localize them to the plasma membrane. We demonstrate here that in neuroblastoma SH-SY5Y cells, brain-specific γ₁-syntrophin binds the neurotrophic factor γ-enolase through its PDZ domain, and translocates it to the plasma membrane, as shown by immunoprecipitation, surface plasmon resonance, fluorescence colocalization and flow cytometry. Extensive colocalization of γ₁-syntrophin and γ-enolase was observed in neurite growth cones in differentiated SH-SY5Y cells. Silencing of the γ₁-syntrophin gene by RNA interference significantly reduced the re-distribution of γ-enolase to the plasma membrane and impaired its neurotrophic effects. We demonstrated that an intact C-terminal end of γ-enolase is essential for its γ₁-syntrophin-assisted trafficking. The cleavage of two amino acids at the C-terminal end of γ-enolase by the carboxypeptidase cathepsin X prevents binding with the γ₁-syntrophin PDZ domain. Collectively, these data demonstrate that γ₁-syntrophin participates in γ-enolase translocation towards the plasma membrane, a pre-requisite for its neurotrophic activity. By disrupting this γ₁-syntrophin-guided subcellular distribution, cathepsin X reduces γ-enolase-induced neurotrophic signaling.

【 授权许可】

CC BY-NC-ND