Department of Cell and Developmental Biology, Vanderbilt University, Nashville, TN 37232, USA.
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA; Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA.
Cell Rep. 2020 Dec 22;33(12):108526. doi: 10.1016/j.celrep.2020.108526.
Many eukaryotes assemble an actin- and myosin-based cytokinetic ring (CR) on the plasma membrane (PM) for cell division, but how it is anchored there remains unclear. In Schizosaccharomyces pombe, the F-BAR protein Cdc15 links the PM via its F-BAR domain to proteins in the CR's interior via its SH3 domain. However, Cdc15's F-BAR domain also directly binds formin Cdc12, suggesting that Cdc15 may polymerize a protein network directly adjacent to the membrane. Here, we determine that the F-BAR domain binds Cdc12 using residues on the face opposite its membrane-binding surface. These residues also bind paxillin-like Pxl1, promoting its recruitment with calcineurin to the CR. Mutation of these F-BAR domain residues results in a shallower CR, with components localizing ∼35% closer to the PM than in wild type, and aberrant CR constriction. Thus, F-BAR domains serve as oligomeric membrane-bound platforms that can modulate the architecture of an entire actin structure.
许多真核生物在质膜（PM）上组装一个由肌动蛋白和肌球蛋白组成的细胞分裂胞质环（CR），但它如何锚定在那里尚不清楚。在酿酒酵母中，F-BAR 蛋白 Cdc15 通过其 F-BAR 结构域与 CR 内部的蛋白质连接，通过其 SH3 结构域与 PM 连接。然而，Cdc15 的 F-BAR 结构域也直接结合形成蛋白 Cdc12，这表明 Cdc15 可能在膜的直接相邻处聚合一个蛋白质网络。在这里，我们确定 F-BAR 结构域通过其膜结合表面对面的残基与 Cdc12 结合。这些残基还与类似于桩蛋白的 Pxl1 结合，促进其与钙调神经磷酸酶一起被募集到 CR。这些 F-BAR 结构域残基的突变导致 CR 变浅，其成分比野生型更靠近 PM 约 35%，并且 CR 收缩异常。因此，F-BAR 结构域充当多聚体膜结合平台，可调节整个肌动蛋白结构的结构。
