Rab11-Rab8 cascade dynamics in primary cilia and membrane tubules.

IF 7.5 1区 生物学 Q1 CELL BIOLOGY
Ipsita Saha, Christine Insinna, Christopher J Westlake
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引用次数: 0

Abstract

The Rab11-Rab8 cascade mediated by the Rab8 guanine nucleotide exchange factor (GEF), Rabin8, orchestrates multiple membrane transport processes, but Rab membrane loading and exchange dynamics are unclear. Here, we use advanced fluorescence imaging approaches to characterize Rab11, Rab8, and Rabin8 protein dynamics. Using fluorescence ablation and recovery studies (FRAP), we show that Rab8 ciliary trafficking requires Rab11 and Rabin8. Reciprocally, we discover that Rab11 is recruited to cilia during ciliogenesis in association with Rab8. We uncover a requirement for this cascade in Rab8 association with long tubular membranes (LTMs) in human cells and zebrafish embryos. Membrane exchange dynamics of Rab11 on Rab8 LTMs is shown using super-resolution imaging, along with a dependency on Rabin8 GEF activity. Finally, cascade-dependent Rab8 loading onto enlarged Rab11-Rabin8 membrane structures is discussed. This study demonstrates that the Rab11-Rab8 cascade involves membrane conversion and expands our understanding of the cellular multifunctionality of this trafficking pathway.

初级纤毛和膜管中的 Rab11-Rab8 级联动力学
由 Rab8 鸟嘌呤核苷酸交换因子(GEF)Rabin8 介导的 Rab11-Rab8 级联协调了多种膜转运过程,但 Rab 膜装载和交换动力学尚不清楚。在这里,我们使用先进的荧光成像方法来描述 Rab11、Rab8 和 Rabin8 蛋白的动态特性。利用荧光消融和恢复研究(FRAP),我们发现 Rab8 的纤毛运输需要 Rab11 和 Rabin8。反过来,我们发现 Rab11 在纤毛发生过程中与 Rab8 一起被招募到纤毛上。我们发现,在人体细胞和斑马鱼胚胎中,Rab8 与长管膜(LTMs)的结合需要这一级联。利用超分辨率成像技术显示了 Rab8 LTM 上 Rab11 的膜交换动力学,以及对 Rabin8 GEF 活性的依赖性。最后,还讨论了依赖级联的 Rab8 装载到扩大的 Rab11-Rabin8 膜结构上的问题。这项研究表明,Rab11-Rab8 级联涉及膜转换,并拓展了我们对这一转运途径的细胞多功能性的认识。
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来源期刊
Cell reports
Cell reports CELL BIOLOGY-
CiteScore
13.80
自引率
1.10%
发文量
1305
审稿时长
77 days
期刊介绍: Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.
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