The actin nucleation promoting factor WASH facilitates clathrin-independent endocytosis of human papillomaviruses.

IF 6.2 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

EMBO Reports Pub Date : 2025-10-10 DOI:10.1038/s44319-025-00594-3

Pia Brinkert, Lena Krebs, Pilar Samperio Ventayol, Lilo Greune, Carina Bannach, Cynthia Amakiri, Delia Bucher, Jana Kollasser, Petra Dersch, Steeve Boulant, Theresia E B Stradal, Mario Schelhaas

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Abstract

Endocytosis is a fundamental cellular process facilitated by diverse mechanisms. Remarkably, several distinct clathrin-independent endocytic processes have been identified and characterized following virus uptake into cells. For some, however, mechanistic execution and biological function remain largely unclear. This includes an endocytic process exploited by human papillomavirus type 16 (HPV16). Using HPV16, we examine how vesicles are formed by combining systematic cellular perturbations with electron and video microscopy. Cargo uptake occurs by uncoated, inward-budding pits. Mechanistically, vesicle scission is facilitated by actin polymerization controlled through the actin nucleation-promoting factor WASH. While WASH typically functions in conjunction with the retromer complex on endosomes during retrograde trafficking, endocytic vesicle formation is largely independent of retromer itself and the heterodimeric membrane-bending SNX-BAR retromer adaptor, thereby uncovering a role of WASH in endocytosis in addition to its canonical role in intracellular membrane trafficking.

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肌动蛋白成核促进因子WASH促进人乳头瘤病毒不依赖网格蛋白的内吞作用。

胞吞作用是一个由多种机制促进的基本细胞过程。值得注意的是，在病毒进入细胞后，已经鉴定和表征了几种不同的不依赖网格蛋白的内吞过程。然而，对一些人来说，机制执行和生物学功能在很大程度上仍然不清楚。这包括16型人乳头瘤病毒（HPV16）利用的内吞过程。使用HPV16，我们通过结合电子和视频显微镜系统的细胞扰动来研究囊泡是如何形成的。货物吸收发生在未涂覆的，向内萌芽的坑。在机制上，通过肌动蛋白成核促进因子WASH控制的肌动蛋白聚合促进了囊泡的分裂。虽然在逆行转运过程中，WASH通常与核内体上的反转录复合体一起起作用，但内吞囊泡的形成在很大程度上独立于反转录复合体本身和异二聚体的膜弯曲SNX-BAR反转录复合体，从而揭示了除了在细胞膜内转运中发挥典型作用外，WASH在内吞作用中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EMBO Reports 生物-生化与分子生物学

CiteScore

11.20

自引率

1.30%

发文量

267

审稿时长

1 months

期刊介绍： EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings. The journal's scope includes both long and short-format papers, catering to different types of research contributions. It values studies that: Communicate major findings: Articles that report significant discoveries or advancements in the understanding of biological processes at the molecular, cellular, and developmental levels. Confirm important findings: Research that validates or supports existing knowledge in the field, reinforcing the reliability of previous studies. Refute prominent claims: Studies that challenge or disprove widely accepted ideas or hypotheses in the biosciences, contributing to the correction and evolution of scientific understanding. Present null data: Papers that report negative results or findings that do not support a particular hypothesis, which are crucial for the scientific process as they help to refine or redirect research efforts. EMBO Reports is dedicated to maintaining high standards of scientific rigor and integrity, ensuring that the research it publishes contributes meaningfully to the advancement of knowledge in the life sciences. By covering a broad spectrum of topics and encouraging the publication of both positive and negative results, the journal plays a vital role in promoting a comprehensive and balanced view of scientific inquiry.