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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年10月10日

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  • 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

摘要

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.