Schueler-Furman Ora, Glick Eitan, Segovia José, Linial Michal
Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
Trends Pharmacol Sci. 2006 Feb;27(2):72-7. doi: 10.1016/j.tips.2005.12.004. Epub 2006 Jan 6.
Glial-cell-line-derived neurotrophic factor (GDNF) is a survival and maintenance factor for dopamine-containing neurons and motoneurons. GDNF belongs to a family of structurally related factors that includes neurturin (NRTN), artemin (ARTN) and persephin (PSPN). An initial step in the activation of signaling via the GDNF family of ligands (GFLs) is their binding to their cognate co-receptor GFR alpha. GAS1, an apparently unrelated protein, exhibits homology to GFR alpha and thus we hypothesize that GAS1 can serve as an alternative receptor for GFLs. The functional similarity between GFR alpha and GAS1 extends to their role in embryogenesis, differentiation and glia maintenance, and is substantiated by overlap in their expression profile, subcellular localization and structural details. We propose that the relative expression and localization of the two remote receptors, GFR alpha and GAS1, on the membranes of neuronal and glial cells determines whether these cells survive or undergo apoptotic death.
胶质细胞源性神经营养因子（GDNF）是含多巴胺神经元和运动神经元的存活及维持因子。GDNF属于一个结构相关因子家族，该家族包括神经营养素（NRTN）、Artemin（ARTN）和Persephin（PSPN）。通过GDNF配体家族（GFLs）激活信号传导的初始步骤是它们与同源共受体GFRα结合。GAS1是一种明显无关的蛋白质，与GFRα具有同源性，因此我们推测GAS1可以作为GFLs的替代受体。GFRα和GAS1之间的功能相似性延伸到它们在胚胎发生、分化和神经胶质维持中的作用，并且通过它们的表达谱、亚细胞定位和结构细节的重叠得到证实。我们提出，神经元和神经胶质细胞膜上这两种远距离受体GFRα和GAS1的相对表达和定位决定了这些细胞是存活还是经历凋亡死亡。
