Dynamics of membrane tubulation coupled with fission by a two- component module

• 成果类型: Article
• 署名作者: Bhattacharyya, Soumya; Pucadyil, Thomas J.
• 署名单位: Indian Institute of Science Education & Research (IISER) Pune
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9790
• DOI: 10.1073/pnas.2402180121
• 发表日期: 2024-05-14
• 关键词: domain-containing proteins; bar domain; centronuclear myopathy; crystal-structure; lipid-bilayers; bin1; generation; isoforms; gtpase; planar

摘要

Membrane tubulation coupled with fission (MTCF) is a widespread phenomenon but mechanisms for their coordination remain unclear, partly because of the lack of assays to monitor dynamics of membrane tubulation and subsequent fission. Using polymer cushioned bilayer islands, we analyze the membrane tubulator Bridging Integrator 1 (BIN1) mixed with the fission catalyst dynamin2 (Dyn2). Our results reveal this mixture to constitute a minimal two - component module that demonstrates MTCF. MTCF is an emergent property and arises because BIN1 facilitates recruitment but inhibits membrane binding of Dyn2 in a dose - dependent manner. MTCF is therefore apparent only at high Dyn2 to BIN1 ratios. Because of their mutual involvement in T - tubules biogenesis, mutations in BIN1 and Dyn2 are associated with centronuclear myopathies and our analysis links the pathology with aberrant MTCF. Together, our results establish cushioned bilayer islands as a facile template for the analysis of membrane tubulation and inform of mechanisms that coordinate MTCF.