Insulin (IR) and insulin-like growth factor I (IGF-IR) receptors share structural homology and can form hybrid heterodimers. While different observations suggest that hybrid receptors are important in physiology and pathology, little is known about their function in the brain. To gain further insight into the role of IR/IGF-IR hybrids in this organ, we analyzed their cellular distribution in the mouse brain. We combined proximity ligation assays (PLA) for IR and IGF-IR, a technique that detects close protein-protein interactions, with immunocytochemistry for brain cell markers to identify IR/IGF-IR hybrids in the major types of brain cells. Intriguingly, while all the types of brain cells analyzed co-express both receptors, only neurons, astroglia, and microglia show readily detectable IR/IGF-IR hybrids. Hybrid PLA signal was negligible in brain endothelial cells and was absent in oligodendrocytes. Hybrids were comparatively more abundant in neurons and peaked after brain development was completed. Cell-specific expression and greater abundance in the adult brain suggests specialized actions of IR/IGF-IR hybrids in this organ, particularly in neurons.

胰岛素（IR）和胰岛素样生长因子I（IGF-IR）受体具有结构同源性，可以形成杂合二聚体。尽管不同的观察结果表明杂合受体在生理和病理学中很重要，但对其在大脑中的功能知之甚少。为了进一步了解IR / IGF-IR杂种在此器官中的作用，我们分析了它们在小鼠脑中的细胞分布。我们结合了用于IR和IGF-IR的邻近结扎测定（PLA）（一种检测紧密的蛋白质-蛋白质相互作用的技术）和用于脑细胞标记物的免疫细胞化学技术，以鉴定主要类型的脑细胞中的IR / IGF-IR杂种。有趣的是，尽管分析的所有类型的脑细胞都共同表达两种受体，但只有神经元，星形胶质细胞和小胶质细胞显示出易于检测的IR / IGF-IR杂种。混合PLA信号在脑内皮细胞中可忽略不计，在少突胶质细胞中不存在。杂种在神经元中相对更丰富，并在大脑发育完成后达到顶峰。成年大脑中的细胞特异性表达和更高的丰度表明IR / IGF-IR杂种在该器官中特别是在神经元中的特殊作用。