The F-BAR family of proteins play important roles in many cellular processes by regulating both membrane and actin dynamics. The CIP4 family of F-BAR proteins is widely recognized to function in endocytosis by elongating endocytosing vesicles. However, in primary cortical neurons, CIP4 concentrates at the tips of extending lamellipodia and filopodia and inhibits neurite outgrowth. Here, we report that the highly homologous CIP4 family member, FBP17, induces tubular structures in primary cortical neurons and results in precocious neurite formation. Through domain swapping and deletion experiments, we demonstrate that a novel polybasic region between the F-BAR and HR1 domains is required for membrane bending. Moreover, the presence of a poly-PxxP region in longer splice isoforms of CIP4 and FBP17 largely reverses the localization and function of these proteins. Thus, CIP4 and FBP17 function as an antagonistic pair to fine-tune membrane protrusion, endocytosis, and neurite formation during early neuronal development.

中文翻译：

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F-BAR蛋白在神经元膜突出，肾小管形成和神经突生长中的相反功能。

F-BAR蛋白家族通过调节膜和肌动蛋白的动力学，在许多细胞过程中发挥重要作用。F-BAR蛋白的CIP4家族被广泛认为可通过延长内吞囊泡在内吞作用中发挥作用。然而，在原代皮层神经元中，CIP4集中在延伸的lamellipodia和filopodia的尖端，并抑制神经突的长出。在这里，我们报告高度同源的CIP4家族成员FBP17诱导初级皮层神经元的管状结构，并导致早熟的神经突形成。通过域交换和删除实验，我们证明F-BAR和HR1域之间的新型多元区域是膜弯曲所必需的。此外，CIP4和FBP17的较长剪接同工型中存在poly-PxxP区，在很大程度上逆转了这些蛋白的定位和功能。因此，CIP4和FBP17在早期神经元发育过程中起拮抗作用，可微调膜的突出，内吞作用和神经突的形成。