PDF(Pubmed)
Abstract：
The photoreceptor outer segment is a modified cilium filled with hundreds of flattened \"disc\" membranes responsible for efficient light capture. To maintain photoreceptor health and functionality, outer segments are continuously renewed through the addition of new discs at their base. This process is driven by branched actin polymerization nucleated by the Arp2/3 complex. To induce actin polymerization, Arp2/3 requires a nucleation promoting factor. Here, we show that the nucleation promoting factor driving disc morphogenesis is the pentameric WAVE complex and identify all protein subunits of this complex. We further demonstrate that the knockout of one of them, WASF3, abolishes actin polymerization at the site of disc morphogenesis leading to formation of disorganized membrane lamellae emanating from the photoreceptor cilium instead of an outer segment. These data establish that, despite the intrinsic ability of photoreceptor ciliary membranes to form lamellar structures, WAVE-dependent actin polymerization is essential for organizing these membranes into a proper outer segment.
摘要：
感光体外段是一个修饰的纤毛，填充了数百个扁平的“圆盘”膜，负责有效地捕获光。为了保持感光器的健康和功能，外部部分通过在其基础上添加新的光盘不断更新。该过程由Arp2/3复合物成核的支化肌动蛋白聚合驱动。为了诱导肌动蛋白聚合，Arp2/3需要成核促进因子。这里,我们证明了驱动椎间盘形态发生的成核促进因子是五聚体WAVE复合物，并鉴定了该复合物的所有蛋白质亚基。我们进一步证明了其中一个的击倒，WASF3消除了椎间盘形态发生部位的肌动蛋白聚合，导致形成从感光纤毛而不是外段发出的杂乱无章的膜薄片。这些数据证明，尽管光感受器睫状膜具有形成层状结构的内在能力，依赖于波的肌动蛋白聚合对于将这些膜组织成适当的外节段至关重要。
