Control of membrane dynamics by cooperative action of bacterial dynamin-like proteins and flotillins

通过细菌动力蛋白和弗洛林斯的协同作用控制膜动力学

• 批准号: 234082876
• 负责人: Professor Dr. Marc Bramkamp
• 金额: --
• 依托单位: Institut für Allgemeine Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/234082876?language=en
• 关键词: Control; membrane; dynamics; cooperative; action

Proteins and lipids are heterogeneously distributed in biological membranes. Correct function of membrane proteins often depends on spatio-temporal organization into defined membrane areas. However, the lateral organization of the bacterial cell membrane has not been analyzed in detail and the influence on cellular processes such as cytokinesis and development remains largely unknown. We have already identified a bacterial flotillin that resides in membrane micro-domains and may contribute to lateral membrane organisation. Flotillins are raft marker proteins which are extensively modified on posttranslational level. These proteins assemble into oligomeric complexes which likely regulates their function. Using the anisotropic dye Laurdan, we have been able to show that bacterial flotillins directly influence membrane order, likely by preventing coalescence of liquid ordered regions. We will analyse how bacterial flotillin homologues in Bacillus subtilis are able to mediate spatial membrane organization and how this impacts function of membrane integral protein machineries such as the secretion system. In addition we have identified a bacterial dynamin-like protein, DynA that binds in a nucleotide-independent manner to negatively charged phospholipids. DynA is involved in membrane tethering and fusion. DynA localizes to septa and may contribute to efficient septum closure. DynA self-organizes into dynamic protein assemblies on membrane surfaces, thereby leading to membrane fusion. This process does not need GTP hydrolysis. Amazingly, we have evidence that DynA may be involved in phage resistance. Hence, similar to the related Mx proteins in vertebrates, bacterial dynamins could be part of a bacterial innate immune system against viral infection. We will study how DynA mediates membrane fusion by ordered complex formation and how this complex is disassembled after membrane fusion. Further we will clarify the cellular role of bacterial dynamins.

蛋白质和脂质不均匀地分布在生物膜中。膜蛋白的正确功能通常取决于时空组织成限定的膜区域。然而，细菌细胞膜的横向组织尚未被详细分析，对细胞过程如胞质分裂和发育的影响在很大程度上仍然未知。我们已经确定了一种细菌flotillin，驻留在膜微域，并可能有助于侧膜组织。Flotillin是一种在翻译后水平上被广泛修饰的筏标记蛋白。这些蛋白质组装成可能调节其功能的寡聚复合物。使用各向异性染料Laurdan，我们已经能够表明，细菌flotillins直接影响膜秩序，可能是通过防止液体有序区域的聚结。我们将分析枯草芽孢杆菌中的细菌flotillin同系物如何能够介导空间膜组织，以及这如何影响膜整合蛋白机器（如分泌系统）的功能。此外，我们已经确定了一种细菌动力蛋白样蛋白，DynA，结合在一个核苷酸独立的方式带负电荷的磷脂。DynA参与膜系留和融合。DynA定位于间隔，可能有助于有效的间隔闭合。DynA在膜表面自组织成动态蛋白质组装体，从而导致膜融合。这个过程不需要GTP水解。令人惊讶的是，我们有证据表明DynA可能参与噬菌体抗性。因此，类似于脊椎动物中的相关Mx蛋白，细菌动力蛋白可能是细菌抵抗病毒感染的先天免疫系统的一部分。我们将研究DynA如何通过有序的复合物形成介导膜融合，以及膜融合后该复合物如何分解。进一步，我们将阐明细菌动力蛋白的细胞作用。