Steady-state regulation of COPII-dependent secretory cargo sorting by inositol trisphosphate receptors, calcium, and penta EF hand proteins.
Steady-state regulation of COPII-dependent secretory cargo sorting by inositol trisphosphate receptors, calcium, and penta EF hand proteins.
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DOI：
10.1016/j.jbc.2023.105471
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发表时间：
2023-12
影响因子：
4.8
通讯作者：
Hay, Jesse C.
中科院分区：
文献类型：
--
作者：
Held, Aaron;Lapka, Jacob;Sargeant, John;Hojanazarova, Jennet;Shaheen, Alaa;Galindo, Samuel;Madreiter-Sokolowski, Corina;Malli, Roland;Graier, Wolfgang F.;Hay, Jesse C.
最近，我们证明了激动剂刺激的涉及IP 3受体的Ca 2+信号传导通过激活penta-EF Hand蛋白质凋亡相关基因-2（ALG-2）和peflin调节ER输出速率。然而，目前尚不清楚IP 3Rs和penta-EF蛋白是否在稳态下调节ER输出速率。在这里，我们测试了这一想法在正常大鼠肾上皮细胞的IP 3R亚型表达的操纵。在标准的生长条件下，自发的胞内钙离子振荡同时发生在连续组的连续细胞，产生细胞间的钙离子波，周期性地跨越单层移动。消耗IP 3R-3，通常是最不混杂的IP 3R亚型，导致增加细胞参与细胞间Ca 2+波在未刺激的细胞。增加的自发信号传导足以引起增加的ALG-2和COPII外壳亚基Sec 31 A和减少的peflin在ER出口位点的定位，导致COPII客户货物VSV-G的ER至高尔基体转运增加。升高的内质网到高尔基体的运输引起了更大的浓度VSV-G在内质网出口网站和运输VSV-G和散装流量货物的相互影响，虽然这两种货物同样需要Sec 31 A。使用4-苯基丁酸盐的客户货物分拣的灭活对客户和批量流动货物具有相反的相互作用，并且中和了ALG-2活化对运输的任何影响。这项工作扩展了我们对ALG-2机制的了解，并表明在正常大鼠肾细胞中，IP 3R亚型调节稳态Ca 2+信号传导，有助于确定COPII依赖性货物分选的基础分泌速率和严格性。
Recently, we demonstrated that agonist-stimulated Ca2+ signaling involving IP3 receptors modulates ER export rates through activation of the penta-EF Hand proteins apoptosis-linked gene-2 (ALG-2) and peflin. It is unknown, however, whether IP3Rs and penta-EF proteins regulate ER export rates at steady state. Here we tested this idea in normal rat kidney epithelial cells by manipulation of IP3R isoform expression. Under standard growth conditions, spontaneous cytosolic Ca2+ oscillations occurred simultaneously in successive groups of contiguous cells, generating intercellular Ca2+ waves that moved across the monolayer periodically. Depletion of IP3R-3, typically the least promiscuous IP3R isoform, caused increased cell participation in intercellular Ca2+ waves in unstimulated cells. The increased spontaneous signaling was sufficient to cause increased ALG-2 and COPII coat subunit Sec31A and decreased peflin localization at ER exit sites, resulting in increased ER-to-Golgi transport of the COPII client cargo VSV-G. The elevated ER-to-Golgi transport caused greater concentration of VSV-G at ER exit sites and had reciprocal effects on transport of VSV-G and a bulk-flow cargo, though both cargos equally required Sec31A. Inactivation of client cargo sorting using 4-phenylbutyrate had opposing reciprocal effects on client and bulk-flow cargo and neutralized any effect of ALG-2 activation on transport. This work extends our knowledge of ALG-2 mechanisms and indicates that in normal rat kidney cells, IP3R isoforms regulate homeostatic Ca2+ signaling that helps determine the basal secretion rate and stringency of COPII-dependent cargo sorting.
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影响因子：
4
作者：
Chakraborty S;Deb BK;Chorna T;Konieczny V;Taylor CW;Hasan G
通讯作者：
Hasan G
DOI：
10.1002/hep.30228
发表时间：
2019-03
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Franca A;Carlos Melo Lima Filho A;Guerra MT;Weerachayaphorn J;Loiola Dos Santos M;Njei B;Robert M;Xavier Lima C;Vieira Teixeira Vidigal P;Banales JM;Ananthanarayanam M;Leite MF;Nathanson MH
通讯作者：
Nathanson MH
影响因子：
16.6
作者：
Dong, Yunzhou;Lee, Yang;Chen, Hong
通讯作者：
Chen, Hong
影响因子：
4.8
作者：
Hattori, M;Suzuki, AZ;Mikoshiba, K
通讯作者：
Mikoshiba, K
影响因子：
4.8
作者：
Hammadi, Mehdi;Oulidi, Agathe;Van Coppenolle, Fabien
通讯作者：
Van Coppenolle, Fabien