Syndapin/SDPN-1 is required for endocytic recycling and endosomal actin association in the C. elegans intestine.
Syndapin/SDPN-1 is required for endocytic recycling and endosomal actin association in the C. elegans intestine.
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DOI：
10.1091/mbc.e16-02-0116
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发表时间：
2016-09-14
影响因子：
3.3
通讯作者：
Grant BD
中科院分区：
文献类型：
--
作者：
Gleason AM;Nguyen KC;Hall DH;Grant BD
f - bar结构域蛋白syndapin的体内分析表明，它调节秀丽隐杆线虫肠道跨膜货物的基侧再循环。SDPN-1可能促进获得再循环核内体特征的早期核内体膜的裂变，允许货物离开早期核内体。Syndapin/pascin家族F-BAR结构域蛋白直接与膜脂结合，并与质膜上的肌动蛋白动力学相关。先前的报道也暗示哺乳动物syndapin 2在受体循环过程中的内体功能，但由于其对内吞摄取的早期步骤的影响以及编码哺乳动物syndapin亚型的三个独立基因之间潜在的冗余性，对哺乳动物syndapin 2在哺乳动物系统中假定的再循环功能的精确分析是困难的。我们分析了秀丽隐杆线虫唯一的突触蛋白SDPN-1的内吞运输功能。我们发现SDPN-1是秀丽隐杆线虫肠上皮早期和底外侧循环内体的驻留蛋白，并且SDPN-1缺失突变体显示出基底外侧循环运输阻断的表型。sdn -1突变体积累异常的核内体，这些核内体对早期核内体和再循环核内体标记呈阳性，这些核内体通常是分开的，并且这些核内体积累了高水平的基底外侧再循环货物。此外，我们观察到内体SDPN-1与f -肌动蛋白生物传感器Lifeact的强共定位，并发现SDPN-1的缺失大大减少了早期内体上Lifeact的积累。综上所述，我们的研究结果为syndapin在体内内吞循环中的功能提供了强有力的证据，并表明syndapin通过内体裂变促进运输。
In vivo analysis of the F-BAR–domain protein syndapin indicates that it regulates basolateral recycling of transmembrane cargo in the Caenorhabditis elegans intestine. SDPN-1 may facilitate the fission of membranes from the early endosome that are acquiring recycling endosome characteristics, allowing cargo to exit the early endosome. Syndapin/pascin-family F-BAR domain proteins bind directly to membrane lipids and are associated with actin dynamics at the plasma membrane. Previous reports also implicated mammalian syndapin 2 in endosome function during receptor recycling, but precise analysis of a putative recycling function for syndapin in mammalian systems is difficult because of its effects on the earlier step of endocytic uptake and potential redundancy among the three separate genes that encode mammalian syndapin isoforms. Here we analyze the endocytic transport function of the only Caenorhabditis elegans syndapin, SDPN-1. We find that SDPN-1 is a resident protein of the early and basolateral recycling endosomes in the C. elegans intestinal epithelium, and sdpn-1 deletion mutants display phenotypes indicating a block in basolateral recycling transport. sdpn-1 mutants accumulate abnormal endosomes positive for early endosome and recycling endosome markers that are normally separate, and such endosomes accumulate high levels of basolateral recycling cargo. Furthermore, we observed strong colocalization of endosomal SDPN-1 with the F-actin biosensor Lifeact and found that loss of SDPN-1 greatly reduced Lifeact accumulation on early endosomes. Taken together, our results provide strong evidence for an in vivo function of syndapin in endocytic recycling and suggest that syndapin promotes transport via endosomal fission.