Department of Pharmacology, University of Texas, Southwestern Medical Center, Dallas, TX, USA.
Department of Biochemistry, University of Texas, Southwestern Medical Center, Dallas, TX, USA.
J Cell Biol. 2023 Jun 5;222(6). doi: 10.1083/jcb.202209098. Epub 2023 Apr 7.
Accurate cellular replication balances the biogenesis and turnover of complex structures. In the apicomplexan parasite Toxoplasma gondii, daughter cells form within an intact mother cell, creating additional challenges to ensuring fidelity of division. The apical complex is critical to parasite infectivity and consists of apical secretory organelles and specialized cytoskeletal structures. We previously identified the kinase ERK7 as required for maturation of the apical complex in Toxoplasma. Here, we define the Toxoplasma ERK7 interactome, including a putative E3 ligase, CSAR1. Genetic disruption of CSAR1 fully suppresses loss of the apical complex upon ERK7 knockdown. Furthermore, we show that CSAR1 is normally responsible for turnover of maternal cytoskeleton during cytokinesis, and that its aberrant function is driven by mislocalization from the parasite residual body to the apical complex. These data identify a protein homeostasis pathway critical for Toxoplasma replication and fitness and suggest an unappreciated role for the parasite residual body in compartmentalizing processes that threaten the fidelity of parasite development.
准确的细胞复制平衡了复杂结构的生物发生和周转。在顶复门寄生虫刚地弓形虫中，子细胞在完整的母细胞内形成，这给确保分裂的保真度带来了额外的挑战。顶端复合物对于寄生虫的感染力至关重要，由顶端分泌细胞器和特化的细胞骨架结构组成。我们之前发现激酶 ERK7 是刚地弓形虫中顶端复合物成熟所必需的。在这里，我们定义了刚地弓形虫 ERK7 的相互作用组，包括一个假定的 E3 连接酶 CSAR1。CSAR1 的基因缺失完全抑制了 ERK7 敲低后顶端复合物的丢失。此外，我们表明 CSAR1 通常负责胞质分裂过程中母细胞骨架的周转，其异常功能是由寄生虫残余体从寄生虫残余体向顶端复合物的异常定位驱动的。这些数据确定了一个对于刚地弓形虫复制和适应性至关重要的蛋白质稳态途径，并表明寄生虫残余体在分隔可能威胁寄生虫发育保真度的过程中具有未被认识的作用。
