Fung Connie, Beck Josh R, Robertson Seth D, Gubbels Marc-Jan, Bradley Peter J
Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095-1489, USA.
Mol Biochem Parasitol. 2012 Aug;184(2):99-108. doi: 10.1016/j.molbiopara.2012.05.002. Epub 2012 May 30.
Apicomplexan parasites utilize a peripheral membrane system called the inner membrane complex (IMC) to facilitate host cell invasion and parasite replication. We recently identified a novel family of Toxoplasma IMC Sub-compartment Proteins (ISP1/2/3) that localize to sub-domains of the IMC using a targeting mechanism that is dependent on coordinated myristoylation and palmitoylation of a series of residues in the N-terminus of the protein. While the precise functions of the ISPs are unknown, deletion of ISP2 results in replication defects, suggesting that this family of proteins plays a role in daughter cell formation. Here we have characterized a fourth ISP family member (ISP4) and discovered that this protein localizes to the central IMC sub-compartment, similar to ISP2. Like ISP1/3, ISP4 is dispensable for the tachyzoite lytic cycle as the disruption of ISP4 does not produce any gross replication or growth defects. Surprisingly, targeting of ISP4 to the IMC membranes is dependent on residues predicted for palmitoylation but not myristoylation, setting its trafficking apart from the other ISP proteins and demonstrating distinct mechanisms of protein localization to the IMC membranes, even within a family of highly related proteins.
顶复门寄生虫利用一种称为内膜复合体（IMC）的外周膜系统来促进宿主细胞入侵和寄生虫复制。我们最近鉴定了一个新的弓形虫IMC亚区室蛋白家族（ISP1/2/3），它们通过一种靶向机制定位于IMC的亚区室，该机制依赖于蛋白质N端一系列残基的协同肉豆蔻酰化和棕榈酰化。虽然ISP的确切功能尚不清楚，但ISP2的缺失会导致复制缺陷，这表明该蛋白家族在子细胞形成中起作用。在这里，我们对第四个ISP家族成员（ISP4）进行了表征，发现该蛋白定位于IMC中央亚区室，类似于ISP2。与ISP1/3一样，ISP4对于速殖子裂解周期是可有可无的，因为ISP4的破坏不会产生任何明显的复制或生长缺陷。令人惊讶的是，ISP4定位于IMC膜依赖于预测的棕榈酰化残基，而不是肉豆蔻酰化残基，这使其运输与其他ISP蛋白不同，并证明了即使在高度相关的蛋白家族中，蛋白质定位于IMC膜的机制也不同。
