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突触结合蛋白通过一种意想不到的机制在体内与内吞蛋白协同作用。

Synaptojanin cooperates in vivo with endophilin through an unexpected mechanism.

作者信息

Dong Yongming, Gou Yueyang, Li Yi, Liu Yan, Bai Jihong

机构信息

Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States.

College of Life Science, Sichuan University, Chengdu, China.

出版信息

Elife. 2015 Apr 28;4:e05660. doi: 10.7554/eLife.05660.

DOI:10.7554/eLife.05660
PMID:25918845
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4435004/
Abstract

Synaptojanin and endophilin represent a classic pair of endocytic proteins that exhibit coordinated action during rapid synaptic vesicle endocytosis. Current models suggest that synaptojanin activity is tightly associated with endophilin through high-affinity binding between the synaptojanin proline-rich domain (PRD) and the endophilin SH3 domain. Surprisingly, we find that truncated synaptojanin lacking the PRD domain sustains normal synaptic transmission, indicating that synaptojanin's core function in vivo resides in the remaining two domains that contain phosphoinositide-phosphatase activities: an N-terminal Sac1 phosphatase domain and a 5-phosphatase domain. We further show that the Sac1 domain plays an unexpected role in targeting synaptojanin to synapses. The requirement for Sac1 is bypassed by tethering the synaptojanin 5-phophatase to the endophilin membrane-bending Bin-Amphiphysin-Rvs (BAR) domain. Together, our results uncover an unexpected role for the Sac1 domain in vivo in supporting coincident action between synaptojanin and endophilin at synapses.

摘要

突触素I和内吞蛋白是一对典型的内吞蛋白，在快速突触小泡内吞过程中表现出协同作用。目前的模型表明，突触素I的活性通过其富含脯氨酸结构域（PRD）与内吞蛋白的SH3结构域之间的高亲和力结合而与内吞蛋白紧密相关。令人惊讶的是，我们发现缺失PRD结构域的截短型突触素I能维持正常的突触传递，这表明突触素I在体内的核心功能存在于其余两个具有磷酸肌醇磷酸酶活性的结构域中：一个N端Sac1磷酸酶结构域和一个5-磷酸酶结构域。我们进一步表明，Sac1结构域在将突触素I靶向突触方面发挥了意想不到的作用。通过将突触素I的5-磷酸酶与内吞蛋白的膜弯曲Bin-双栖蛋白-Rvs（BAR）结构域相连，可以绕过对Sac1的需求。总之，我们的结果揭示了Sac1结构域在体内支持突触素I和内吞蛋白在突触处协同作用的意想不到的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4531/4435004/880ebf1a25c7/elife05660fs010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4531/4435004/0952817926f6/elife05660f007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4531/4435004/7e75e6e81093/elife05660fs005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4531/4435004/e5ed3d659372/elife05660f008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4531/4435004/880ebf1a25c7/elife05660fs010.jpg

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2
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