Molecular mechanics underlying flat-to-round membrane budding in live secretory cells

Wonchul Shin, Ben Zucker, Nidhi Kundu, Sung Hoon Lee, Bo Shi, Chung Yu Chan, Xiaoli Guo, Jonathan T. Harrison, Jaymie Moore Turechek, Jenny E. Hinshaw, Michael M. Kozlov, Ling Gang Wu

Research output: Contribution to journalArticlepeer-review

Abstract

Membrane budding entails forces to transform flat membrane into vesicles essential for cell survival. Accumulated studies have identified coat-proteins (e.g., clathrin) as potential budding factors. However, forces mediating many non-coated membrane buddings remain unclear. By visualizing proteins in mediating endocytic budding in live neuroendocrine cells, performing in vitro protein reconstitution and physical modeling, we discovered how non-coated-membrane budding is mediated: actin filaments and dynamin generate a pulling force transforming flat membrane into Λ-shape; subsequently, dynamin helices surround and constrict Λ-profile’s base, transforming Λ- to Ω-profile, and then constrict Ω-profile’s pore, converting Ω-profiles to vesicles. These mechanisms control budding speed, vesicle size and number, generating diverse endocytic modes differing in these parameters. Their impact is widespread beyond secretory cells, as the unexpectedly powerful functions of dynamin and actin, previously thought to mediate fission and overcome tension, respectively, may contribute to many dynamin/actin-dependent non-coated-membrane buddings, coated-membrane buddings, and other membrane remodeling processes.

Original languageEnglish
Article number3697
JournalNature Communications
Volume13
Issue number1
DOIs
StatePublished - Dec 2022

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