RAB22A 将上皮细胞生长因子受体(EGFR)从早期内体运送到循环内体,以释放微囊。

IF 15.5 1区 医学 Q1 CELL BIOLOGY Journal of Extracellular Vesicles Pub Date : 2024-07-25 DOI:10.1002/jev2.12494
Yujie Lin, Denghui Wei, Xiaobo He, Lanqing Huo, Jingxuan Wang, Xia Zhang, Yuanzhong Wu, Ruhua Zhang, Ying Gao, Tiebang Kang
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引用次数: 0

摘要

含有蛋白质、核酸或细胞器的微囊泡(MV)从质膜上脱落。尽管微囊泡出芽的机制已被很好地阐明,但人们对内质体转运与微囊泡形成之间的联系仍然知之甚少。在本报告中,通过对 RAB GTPase 家族的筛选,发现 RAB22A 对含表皮生长因子受体的 MV 的形成至关重要。RAB22A 招募 RAB7A 的 GTP 酶激活蛋白(GAP)TBC1D2B,使 RAB7A 失活,从而阻止表皮生长因子受体被转运到晚期内体和溶酶体。RAB22A 还与 RAB11A 的鸟嘌呤核苷酸交换因子(GEF)SH3BP5L 结合,激活早期内体上的 RAB11A。因此,表皮生长因子受体被回收到细胞表面,并被包装成膜质。此外,表皮生长因子受体还能使 RAB22A 在 Tyr136 处磷酸化,进而促进含表皮生长因子受体的 MV 的形成。我们的研究结果表明,RAB22A 可作为早期内体的分拣器,通过激活 RAB11A 和使 RAB7A 失活,将表皮生长因子受体分拣到循环内体以脱落 MV。
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RAB22A sorts epithelial growth factor receptor (EGFR) from early endosomes to recycling endosomes for microvesicles release

Microvesicles (MVs) containing proteins, nucleic acid or organelles are shed from the plasma membrane. Although the mechanisms of MV budding are well elucidated, the connection between endosomal trafficking and MV formation remains poorly understood. In this report, RAB22A is revealed to be crucial for EGFR-containing MVs formation by the RAB GTPase family screening. RAB22A recruits TBC1D2B, a GTPase-activating protein (GAP) of RAB7A, to inactivate RAB7A, thus preventing EGFR from being transported to late endosomes and lysosomes. RAB22A also engages SH3BP5L, a guanine-nucleotide exchange factor (GEF) of RAB11A, to activate RAB11A on early endosomes. Consequently, EGFR is recycled to the cell surface and packaged into MVs. Furthermore, EGFR can phosphorylate RAB22A at Tyr136, which in turn promotes EGFR-containing MVs formation. Our findings illustrate that RAB22A acts as a sorter on early endosomes to sort EGFR to recycling endosomes for MV shedding by both activating RAB11A and inactivating RAB7A.

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来源期刊
Journal of Extracellular Vesicles
Journal of Extracellular Vesicles Biochemistry, Genetics and Molecular Biology-Cell Biology
CiteScore
27.30
自引率
4.40%
发文量
115
审稿时长
12 weeks
期刊介绍: The Journal of Extracellular Vesicles is an open access research publication that focuses on extracellular vesicles, including microvesicles, exosomes, ectosomes, and apoptotic bodies. It serves as the official journal of the International Society for Extracellular Vesicles and aims to facilitate the exchange of data, ideas, and information pertaining to the chemistry, biology, and applications of extracellular vesicles. The journal covers various aspects such as the cellular and molecular mechanisms of extracellular vesicles biogenesis, technological advancements in their isolation, quantification, and characterization, the role and function of extracellular vesicles in biology, stem cell-derived extracellular vesicles and their biology, as well as the application of extracellular vesicles for pharmacological, immunological, or genetic therapies. The Journal of Extracellular Vesicles is widely recognized and indexed by numerous services, including Biological Abstracts, BIOSIS Previews, Chemical Abstracts Service (CAS), Current Contents/Life Sciences, Directory of Open Access Journals (DOAJ), Journal Citation Reports/Science Edition, Google Scholar, ProQuest Natural Science Collection, ProQuest SciTech Collection, SciTech Premium Collection, PubMed Central/PubMed, Science Citation Index Expanded, ScienceOpen, and Scopus.
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