Morphogenesis of many protozoans depends on a polarized establishment of cytoskeletal structures. In malaria‐causing parasites, this can be observed when a round zygote develops into an elongated motile ookinete within the mosquito stomach. This morphogenesis is mediated by the pellicle cytoskeletal structures, including the inner membrane complex (IMC) and the underlying subpellicular microtubules (SPMs). How the parasite maintains the IMC‐SPM connection and establishes a dome‐like structure of SPM to support cell elongation is unclear. Here, we show that palmitoylation of N‐terminal cysteines of two IMC proteins (ISP1/ISP3) regulates the IMC localization of ISP1/ISP3 and zygote‐to‐ookinete differentiation. Palmitoylation of ISP1/ISP3 is catalyzed by an IMC‐residing palmitoyl‐S‐acyl‐transferase (PAT) DHHC2. Surprisingly, DHHC2 undergoes self‐palmitoylation at C‐terminal cysteines via its PAT activity, which controls DHHC2 localization in IMC after zygote formation. IMC‐anchored ISP1 and ISP3 interact with microtubule component β‐tubulin, serving as tethers to maintain the proper structure of SPM during zygote elongation. This study identifies the first PAT–substrate pair in malaria parasites and uncovers a protein palmitoylation cascade regulating microtubule cytoskeleton.

中文翻译：

---

蛋白质棕榈酰化级联调节疟原虫中的微管细胞骨架完整性。

许多原生动物的形态发生取决于细胞骨架结构的极化建立。在引起疟疾的寄生虫中，当圆形受精卵在蚊子胃内发育成细长的活动动体时，可以观察到这一点。这种形态发生由薄膜细胞骨架结构介导，包括内膜复合物 (IMC) 和底层的亚薄膜微管 (SPM)。寄生虫如何维持 IMC-SPM 连接并建立 SPM 的圆顶状结构以支持细胞伸长尚不清楚。在这里，我们表明两种 IMC 蛋白 (ISP1/ISP3) 的 N 端半胱氨酸的棕榈酰化调节了 ISP1/ISP3 的 IMC 定位和受精卵到激动素的分化。ISP1/ISP3 的棕榈酰化由驻留在 IMC 的棕榈酰-S-酰基转移酶 (PAT) DHHC2 催化。出奇，DHHC2 通过其 PAT 活性在 C 端半胱氨酸处进行自我棕榈酰化，这控制着受精卵形成后 DHHC2 在 IMC 中的定位。IMC 锚定的 ISP1 和 ISP3 与微管成分 β-微管蛋白相互作用，在受精卵伸长过程中作为系链维持 SPM 的正确结构。这项研究确定了疟疾寄生虫中的第一个 PAT-底物对，并揭示了调节微管细胞骨架的蛋白质棕榈酰化级联反应。