School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067, India.
School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067, India.
J Biol Chem. 2018 Aug 3;293(31):12222-12238. doi: 10.1074/jbc.RA117.001225. Epub 2018 Jun 15.
The ability of to switch between yeast to hyphal form is a property that is primarily associated with the invasion and virulence of this human pathogenic fungus. Several glycosylphosphatidylinositol (GPI)-anchored proteins are expressed only during hyphal morphogenesis. One of the major pathways that controls hyphal morphogenesis is the Ras-signaling pathway. We examine the cross-talk between GPI anchor biosynthesis and Ras signaling in We show that the first step of GPI biosynthesis is activated by Ras in This is diametrically opposite to what is reported in Of the two Ras proteins, CaRas1 alone activates GPI-GnT activity; activity is further stimulated by constitutively activated CaRas1. CaRas1 localized to the cytoplasm or endoplasmic reticulum (ER) is sufficient for GPI-GnT activation. Of the six subunits of the GPI--acetylglucosaminyltransferase (GPI-GnT) that catalyze the first step of GPI biosynthesis, CaGpi2 is the key player involved in activating Ras signaling and hyphal morphogenesis. Activation of Ras signaling is independent of the catalytic competence of GPI-GnT. This too is unlike what is observed in where multiple subunits were identified as inhibiting Ras2. Fluorescence resonance energy transfer (FRET) studies indicate a specific physical interaction between CaRas1 and CaGpi2 in the ER, which would explain the ability of CaRas1 to activate GPI-GnT. CaGpi2, in turn, promotes activation of the Ras-signaling pathway and hyphal morphogenesis. The mutant is also more susceptible to macrophage-mediated killing, and macrophage cells show better survival when co-cultured with .
的从酵母形态到菌丝形态的转变能力主要与这种人类致病性真菌的侵袭和毒力有关。几种糖基磷脂酰肌醇（GPI）锚定蛋白仅在菌丝形态发生时表达。控制菌丝形态发生的主要途径之一是 Ras 信号通路。我们检查了 GPI 锚生物合成和 Ras 信号之间的串扰在中。我们表明，GPI 生物合成的第一步被 Ras 在中激活。这与在中报道的完全相反。在两种 Ras 蛋白中，仅 CaRas1 激活 GPI-GnT 活性；活性进一步被组成性激活的 CaRas1 刺激。CaRas1 定位于细胞质或内质网 (ER) 足以激活 GPI-GnT。催化 GPI 生物合成第一步的六个 GPI--乙酰葡萄糖胺转移酶 (GPI-GnT) 亚基中，CaGpi2 是参与激活 Ras 信号和菌丝形态发生的关键参与者。Ras 信号的激活独立于 GPI-GnT 的催化能力。这与在中观察到的情况不同，在中，多个亚基被鉴定为抑制 Ras2。荧光共振能量转移 (FRET) 研究表明，CaRas1 和 CaGpi2 在 ER 中存在特定的物理相互作用，这可以解释 CaRas1 激活 GPI-GnT 的能力。反过来，CaGpi2 促进 Ras 信号通路的激活和菌丝形态发生。突变体也更容易被巨噬细胞介导的杀伤，并且当与共培养时，巨噬细胞显示出更好的存活。
