关键词: BAR domain–containing proteins dynamin membrane fission membrane tubulation polymer cushions

Mesh : Dynamin II / metabolism genetics Humans Adaptor Proteins, Signal Transducing / metabolism genetics Tumor Suppressor Proteins / metabolism genetics Cell Membrane / metabolism Nuclear Proteins / metabolism genetics Mitochondrial Dynamics / physiology Myopathies, Structural, Congenital / genetics metabolism

来  源:   DOI:10.1073/pnas.2402180121   PDF(Pubmed)

Abstract:
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.
摘要:
膜管结合裂变(MTCF)是一种普遍现象,但它们的协调机制尚不清楚。部分原因是缺乏监测膜管动态和随后裂变的分析方法。使用聚合物缓冲双层岛,我们分析了与裂变催化剂dynamin2(Dyn2)混合的膜微管器桥接积分器1(BIN1)。我们的结果表明,这种混合物构成了一个最小的双组分模块,证明了MTCF。MTCF是一种新兴特性,由于BIN1促进募集,但以剂量依赖性方式抑制Dyn2的膜结合而产生。因此MTCF仅在高Dyn2与BIN1比率下是明显的。由于它们共同参与T-小管的生物发生,BIN1和Dyn2的突变与核中心性肌病相关,我们的分析将病理学与异常MTCF联系起来.一起,我们的结果建立了缓冲双层岛作为分析膜管的简单模板,并告知协调MTCF的机制。
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