Program in Cellular Neuroscience, Neurodegeneration and Repair, Department of Cell Biology, Yale University School of Medicine, P.O. Box 9812, New Haven, CT 06536-0812, USA.
Cell. 2013 Jul 18;154(2):337-50. doi: 10.1016/j.cell.2013.06.028.
Synaptic contacts are largely established during embryogenesis and are then maintained during growth. To identify molecules involved in this process, we conducted a forward genetic screen in C. elegans and identified cima-1. In cima-1 mutants, synaptic contacts are correctly established during embryogenesis, but ectopic synapses emerge during postdevelopmental growth. cima-1 encodes a solute carrier in the SLC17 family of transporters that includes sialin, a protein that when mutated in humans results in neurological disorders. cima-1 does not function in neurons but rather functions in the nearby epidermal cells to correctly position glia during postlarval growth. Our findings indicate that CIMA-1 antagonizes the FGF receptor (FGFR), and does so most likely by inhibiting FGFR's role in epidermal-glia adhesion rather than signaling. Our data suggest that epidermal-glia crosstalk, in this case mediated by a transporter and the FGF receptor, is vital to preserve embryonically derived circuit architecture during postdevelopmental growth.
突触联系在胚胎发生期间基本建立，然后在生长过程中得到维持。为了鉴定参与这一过程的分子，我们在秀丽隐杆线虫中进行了正向遗传筛选，并鉴定出 cima-1。在 cima-1 突变体中，突触联系在胚胎发生期间正确建立，但在发育后生长期间出现异位突触。cima-1 编码溶质载体家族的 SLC17 转运体中的一种溶质载体，包括唾液酸，当人类中的该蛋白发生突变时会导致神经紊乱。cima-1 不在神经元中发挥作用，而是在附近的表皮细胞中发挥作用，以便在幼虫后期生长期间正确定位神经胶质。我们的研究结果表明，CIMA-1 拮抗 FGFR（成纤维细胞生长因子受体），最有可能是通过抑制 FGFR 在表皮-胶质黏附中的作用，而不是通过信号转导来实现的。我们的数据表明，表皮-胶质细胞串扰，在这种情况下由转运体和 FGFR 介导，对于在发育后生长过程中维持胚胎衍生的回路结构至关重要。
