RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan. Lipid Biology Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Science. 2015 Aug 28;349(6251):974-7. doi: 10.1126/science.aab3516.
Glycerophospholipids, the structural components of cell membranes, have not been considered to be spatial cues for intercellular signaling because of their ubiquitous distribution. We identified lyso-phosphatidyl-β-D-glucoside (LysoPtdGlc), a hydrophilic glycerophospholipid, and demonstrated its role in modality-specific repulsive guidance of spinal cord sensory axons. LysoPtdGlc is locally synthesized and released by radial glia in a patterned spatial distribution to regulate the targeting of nociceptive but not proprioceptive central axon projections. Library screening identified the G protein-coupled receptor GPR55 as a high-affinity receptor for LysoPtdGlc, and GPR55 deletion or LysoPtdGlc loss of function in vivo caused the misallocation of nociceptive axons into proprioceptive zones. These findings show that LysoPtdGlc/GPR55 is a lipid-based signaling system in glia-neuron communication for neural development.
甘油磷脂是细胞膜的结构成分，由于其广泛分布，它们一直不被认为是细胞间信号传递的空间线索。我们鉴定了溶血磷脂酰-β-D-葡萄糖苷（LysoPtdGlc），一种亲水甘油磷脂，并证明其在脊髓感觉轴突的模态特异性排斥性引导中发挥作用。LysoPtdGlc 由放射状胶质细胞在图案化的空间分布中局部合成和释放，以调节伤害感受性但不 proprioceptive 中央轴突投射的靶向。文库筛选鉴定出 G 蛋白偶联受体 GPR55 为 LysoPtdGlc 的高亲和力受体，并且体内 GPR55 缺失或 LysoPtdGlc 功能丧失导致伤害感受性轴突错误分配到 proprioceptive 区域。这些发现表明 LysoPtdGlc/GPR55 是神经发育中胶质细胞-神经元通讯的基于脂质的信号系统。
