Dscam2 is a cell surface protein required for neuronal development in Drosophila; it can promote neural wiring through homophilic recognition that leads to either adhesion or repulsion between neurites. Here, we report that Dscam2 also plays a post-developmental role in suppressing synaptic strength. This function is dependent on one of two distinct extracellular isoforms of the protein and is autonomous to motor neurons. We link the PI3K enhancer, Centaurin gamma 1A, to the Dscam2-dependent regulation of synaptic strength and show that changes in phosphoinositide levels correlate with changes in endosomal compartments that have previously been associated with synaptic strength. Using transmission electron microscopy, we find an increase in synaptic vesicles at Dscam2 mutant active zones, providing a rationale for the increase in synaptic strength. Our study provides the first evidence that Dscam2 can regulate synaptic physiology and highlights how diverse roles of alternative protein isoforms can contribute to unique aspects of brain development and function.

中文翻译：

---

Dscam2 通过 PI3K 依赖性内体途径抑制突触强度

Dscam2 是果蝇神经元发育所需的细胞表面蛋白；它可以通过同质识别促进神经连接，从而导致神经突之间的粘附或排斥。在此，我们报告 Dscam2 在抑制突触强度方面也发挥着发育后作用。该功能依赖于该蛋白质的两种不同的细胞外亚型之一，并且对于运动神经元来说是自主的。我们将 PI3K 增强子 Centaurin gamma 1A 与 Dscam2 依赖性突触强度调节联系起来，并表明磷酸肌醇水平的变化与内体区室的变化相关，而内体区室以前与突触强度相关。使用透射电子显微镜，我们发现 Dscam2 突变体活性区的突触小泡增加，为突触强度增加提供了理论依据。我们的研究提供了第一个证据，证明 Dscam2 可以调节突触生理学，并强调替代蛋白亚型的不同作用如何促进大脑发育和功能的独特方面。