2026-05-20 九州大学
参考図：急速に拡大する膜構造（ブレブ）の根元に形成される膜陥入構造（SBI）の発見
＜関連情報＞
ブレブの拡張には、湾曲を好むタンパク質を隔離する一時的な膜陥入が必要である Bleb expansion requires transient membrane invaginations that sequester curvature-preferring proteins
Yuki Maekawa, Saori R. Yoshii, Noboru Mizushima, and Junichi Ikenouchi
Proceedings of the National Academy of Sciences Published:May 20, 2026
DOI:https://doi.org/10.1073/pnas.2534871123
Significance
Cells that migrate using blebs must rapidly expand their plasma membrane, yet how they reorganize membrane curvature and proteins during this process has remained unclear. Here, we identify a previously unrecognized membrane structure, the sub-bleb invagination (SBI), which forms at the bleb base during expansion. Using correlative light and electron microscopy, we show that SBIs are membrane invaginations with pronounced positive curvature that selectively sequester curvature-preferring membrane proteins such as Caveolin-1 and Piezo1, preventing their accumulation on the highly convex bleb surface. Notably, overexpression of Caveolin-1 suppresses bleb enlargement and impairs bleb-based amoeboid migration. These findings reveal a curvature-based mechanism that couples membrane remodeling with protein sorting, providing insight into how cells maintain mechanical flexibility during rapid shape changes.
Abstract
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.
