Bleb expansion requires transient membrane invaginations that sequester curvature-preferring proteins

• 成果类型: Article
• 署名作者: Maekawa, Yuki; Yoshii, Saori R.; Mizushima, Noboru; Ikenouchi, Junichi
• 署名单位: Kyushu University; University of Tokyo; University of Tokyo
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2534871123
• 发表日期: 2026-05-26
• 页码: e2534871123
• 关键词: bleb; membrane curvature; plasma membrane invagination; curvature-preferring proteins; Caveolin-1

摘要

Bleb-based cell migration involves rapid plasma membrane expansion driven by intracellular pressure. How the membrane reorganizes its curvature and protein composition during this process remains unclear. Here, we identify a distinct inward membrane structure, termed the sub-bleb invagination (SBI), that forms de novo at the bleb base during expansion. SBIs display strong positive curvature and transiently sequester curvature-preferring integral membrane proteins such as Caveolin-1 and Piezo1 without endocytosis. Live-cell imaging shows that these proteins transiently accumulate at the SBIs in concert with bleb growth, indicating that bleb expansion dynamically redistributes membrane curvature and protein localization. Overexpression of curvature-preferring proteins markedly inhibited bleb enlargement and induced the aberrant formation of SBI-like membrane invaginations, suggesting that their excessive accumulation limits the membrane from unfurling. Our findings reveal a curvature-based mechanism for membrane protein sorting during bleb expansion and highlight how the interplay between membrane curvature and integral membrane protein organization shapes PM dynamics.