Department of Cell Biology, Howard Hughes Medical Institute, Program in Cellular Neuroscience, Neurodegeneration, and Repair, Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06519, USA.
Neuron. 2011 Nov 17;72(4):587-601. doi: 10.1016/j.neuron.2011.08.029.
Endophilin is a membrane-binding protein with curvature-generating and -sensing properties that participates in clathrin-dependent endocytosis of synaptic vesicle membranes. Endophilin also binds the GTPase dynamin and the phosphoinositide phosphatase synaptojanin and is thought to coordinate constriction of coated pits with membrane fission (via dynamin) and subsequent uncoating (via synaptojanin). We show that although synaptojanin is recruited by endophilin at bud necks before fission, the knockout of all three mouse endophilins results in the accumulation of clathrin-coated vesicles, but not of clathrin-coated pits, at synapses. The absence of endophilin impairs but does not abolish synaptic transmission and results in perinatal lethality, whereas partial endophilin absence causes severe neurological defects, including epilepsy and neurodegeneration. Our data support a model in which endophilin recruitment to coated pit necks, because of its curvature-sensing properties, primes vesicle buds for subsequent uncoating after membrane fission, without being critically required for the fission reaction itself.
内收蛋白是一种具有产生和感知曲率特性的膜结合蛋白，参与突触囊泡膜的网格蛋白依赖性内吞作用。内收蛋白还与 GTP 酶 dynamin 和磷酸肌醇磷酸酶 synaptojanin 结合，被认为可以协调包被凹陷的收缩与膜裂变（通过 dynamin）和随后的脱包被（通过 synaptojanin）。我们表明，尽管 synaptojanin 在裂变前被内收蛋白募集到芽颈处，但三种小鼠内收蛋白的敲除导致突触处网格蛋白包被囊泡的积累，但不是网格蛋白包被凹陷的积累。内收蛋白的缺失会损害但不会消除突触传递，并导致围产期致死，而部分内收蛋白的缺失会导致严重的神经缺陷，包括癫痫和神经退行性变。我们的数据支持这样一种模型，即内收蛋白募集到包被凹陷的颈部，由于其曲率感应特性，为膜裂变后随后的脱包被做好准备，而不是对裂变反应本身有严格的要求。
