Apactin is involved in remodeling of the actin cytoskeleton during regulated exocytosis.
Apactin is involved in remodeling of the actin cytoskeleton during regulated exocytosis.
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Apactin 参与调节胞吐作用期间肌动蛋白细胞骨架的重塑。
DOI：
10.1078/0171-9335-00361
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发表时间：
2004
影响因子：
6.6
通讯作者：
DeLisle,RobertC
中科院分区：
文献类型：
--
作者：
Tandon,Chanderdeep;DeLisle,RobertC
Apactin是一种80-kDa的I型膜糖蛋白，来源于前Muclin，前Muclin也是产生酶原颗粒蛋白Muclin的前体。先前的工作表明，apactin被有效地从调节的分泌途径中去除，并靶向胰腺腺泡细胞的富含肌动蛋白的顶端质膜。apactin的胞质尾部（C-Tail）由16个氨基酸组成，具有Thr酪蛋白激酶II和Ser蛋白激酶C磷酸化位点，以及C末端PDZ结合结构域。腺泡细胞的分泌刺激导致apactin的Thr磷酸化减少和Ser磷酸化增加。C-Tail结构域下拉肌动蛋白、ezrin和EBP 50/NHERF以磷酸化依赖性方式的融合肽。HIV TAT-C-Tail融合肽用作活胰腺细胞上的显性阴性构建体以研究对肌动蛋白细胞骨架的影响。在分泌刺激期间，TAT-C-Tail-Thr/Asp磷酸化模拟肽引起肌动蛋白包被的酶原颗粒在顶端表面的增加，而TAT-C-Tail-S/D磷酸化模拟肽引起肌动蛋白细胞骨架的加宽。这些数据表明，刺激介导的Thr去磷酸化允许减少apactin与EBP 50/NHERF的关联，并促进肌动蛋白重塑以包覆酶原颗粒。刺激介导的丝氨酸磷酸化增加apactin与肌动蛋白细胞骨架的结合，保持肌动蛋白微丝在顶端表面的紧密捆绑。因此，apactin参与在调节胞吐期间以由apactin C-尾的磷酸化控制的方式重塑顶端细胞骨架。
Apactin is an 80-kDa type I membrane glycoprotein derived from pro-Muclin, a precursor that also gives rise to the zymogen granule protein Muclin. Previous work showed that apactin is efficiently removed from the regulated secretory pathway and targeted to the actin-rich apical plasma membrane of the pancreatic acinar cell. The cytosolic tail (C-Tail) of apactin consists of 16 amino acids, has Thr casein kinase II and Ser protein kinase C phosphorylation sites, and a C-terminal PDZ-binding domain. Secretory stimulation of acinar cells causes a decrease in Thr phosphorylation and an increase in Ser phosphorylation of apactin. Fusion peptides of the C-Tail domain pulldown actin, ezrin, and EBP50/NHERF in a phosphorylation-dependent manner. HIV TAT-C-Tail fusion peptides were used as dominant negative constructs on living pancreatic cells to study effects on the actin cytoskeleton. During secretory stimulation, TAT-C-Tail-Thr/Asp phosphomimetic peptide caused an increase in actin-coated zymogen granules at the apical surface, while TAT-C-Tail-S/D phosphomimetic peptide caused a broadening of the actin cytoskeleton. These data indicate that stimulation-mediated Thr dephosphorylation allows decreased association of apactin with EBP50/NHERF and fosters actin remodeling to coat zymogen granules. Stimulation-mediated Ser phosphorylation increases apactin association with the actin cytoskeleton, maintaining tight bundling of actin microfilaments at the apical surface. Thus, apactin is involved in remodeling the apical cytoskeleton during regulated exocytosis in a manner controlled by phosphorylation of the apactin C-Tail.