Calcineurin regulates the yeast synaptojanin Inp53/Sjl3 during membrane stress.
Calcineurin regulates the yeast synaptojanin Inp53/Sjl3 during membrane stress.
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DOI：
10.1091/mbc.e14-05-1019
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发表时间：
2015-02-15
影响因子：
3.3
通讯作者：
Cyert MS
中科院分区：
文献类型：
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作者：
Guiney EL;Goldman AR;Elias JE;Cyert MS
高渗休克驱动钙调神经磷酸酶和Inp 53/synaptojanin的重组。钙调磷酸酶在极化生长的位点积累，使Inp 53去磷酸化以维持正常的膜和肌动蛋白细胞骨架形态，并使其从网格蛋白中解离并结合到内吞蛋白Bsp 1、Bzz 1和Sla 1。在高渗休克期间，酿酒酵母适应生理挑战，包括由快速细胞收缩产生的大质膜内陷。钙调磷酸酶，钙离子/钙调蛋白依赖性磷酸酶，通常是胞质，但集中在斑点和在激烈的渗透胁迫过程中的极化生长的网站;钙调磷酸酶激活基因表达的抑制表明，限制其访问基板调谐钙调磷酸酶信号的特异性。高渗休克促进钙调神经磷酸酶与PI（4，5）P2磷酸酶synaptojanin/Inp 53/Sjl 3的结合和去磷酸化，并引起PI（4，5）P2富集膜结构域的显著钙调神经磷酸酶依赖性重组。Inp 53通常促进在trans-Golgi网络的分选，但定位于皮质肌动蛋白补丁在应激细胞。通过激活Inp 53，钙调神经磷酸酶复极化肌动蛋白细胞骨架，并保持正常的质膜形态在synaptojanin有限的细胞。在响应高渗休克和钙调神经磷酸酶依赖性调节，Inp 53的变化，主要与网格蛋白相互作用的内吞蛋白SLA 1，BZZ 1和BSP 1，这表明Inp 53介导的应力特异性内吞事件。这种反应与神经元中钙调神经磷酸酶调节的活性依赖性大量内吞作用具有生理和分子相似性，其检索由突触囊泡融合沉积的质膜团。我们认为，激活Ca 2 +/钙调神经磷酸酶和PI（4，5）P2信号调节内吞作用是一个基本的和保守的反应，在真核细胞膜过量。
Hyperosmotic shock drives a reorganization of calcineurin and Inp53/synaptojanin. Calcineurin accumulates at sites of polarized growth, dephosphorylates Inp53 to maintain normal membrane and actin cytoskeleton morphology, and causes it to dissociate from clathrin and bind to endocytic proteins Bsp1, Bzz1, and Sla1. During hyperosmotic shock, Saccharomyces cerevisiae adjusts to physiological challenges, including large plasma membrane invaginations generated by rapid cell shrinkage. Calcineurin, the Ca2+/calmodulin–dependent phosphatase, is normally cytosolic but concentrates in puncta and at sites of polarized growth during intense osmotic stress; inhibition of calcineurin-activated gene expression suggests that restricting its access to substrates tunes calcineurin signaling specificity. Hyperosmotic shock promotes calcineurin binding to and dephosphorylation of the PI(4,5)P2 phosphatase synaptojanin/Inp53/Sjl3 and causes dramatic calcineurin-dependent reorganization of PI(4,5)P2-enriched membrane domains. Inp53 normally promotes sorting at the trans-Golgi network but localizes to cortical actin patches in osmotically stressed cells. By activating Inp53, calcineurin repolarizes the actin cytoskeleton and maintains normal plasma membrane morphology in synaptojanin-limited cells. In response to hyperosmotic shock and calcineurin-dependent regulation, Inp53 shifts from associating predominantly with clathrin to interacting with endocytic proteins Sla1, Bzz1, and Bsp1, suggesting that Inp53 mediates stress-specific endocytic events. This response has physiological and molecular similarities to calcineurin-regulated activity-dependent bulk endocytosis in neurons, which retrieves a bolus of plasma membrane deposited by synaptic vesicle fusion. We propose that activation of Ca2+/calcineurin and PI(4,5)P2 signaling to regulate endocytosis is a fundamental and conserved response to excess membrane in eukaryotic cells.