Polarized but differential localization and recruitment of STIM1, Orai1 and TRPC channels in secretory cells.
Polarized but differential localization and recruitment of STIM1, Orai1 and TRPC channels in secretory cells.
复制标题
DOI：
10.1111/j.1600-0854.2010.01138.x
复制
发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Muallem S
中科院分区：
文献类型：
--
作者：
Hong JH;Li Q;Kim MS;Shin DM;Feske S;Birnbaumer L;Cheng KT;Ambudkar IS;Muallem S
分泌性上皮细胞的极化Ca2+信号是由Ca2+信号蛋白在顶极的区隔定位决定的。最近，内质网Ca2+传感器STIM1和Orai通道被证明在储存依赖性Ca2+内流中起关键作用。STIM1也控制TRPC通道。在这里，我们询问细胞刺激如何影响极化细胞中天然蛋白的定位、募集和功能。抑制Orai1、STIM1或删除TRPC1可减少Ca2+内流和Ca2+振荡频率。Orai1定位于外侧膜的顶极。令人惊讶的是，细胞刺激不会导致原生Orai1的强大聚类，正如在表达的Orai1中观察到的那样。出乎意料的是，细胞刺激导致原生STIM1极化募集到顶端和外侧区域，从而募集到有或没有Orai1的区域。因此，STIM1和Orai1仅表现出40%的共定位。因此，与Orai1相比，STIM1与基底外侧膜标记物E-cadherin具有更高的共定位，而Orai1与紧密连接蛋白ZO1具有更高的共定位。TRPC1在质膜的顶端和基底外侧表达。STIM1/Orai1/IP3Rs/TRPCs的Co-IP通过细胞刺激增强，并被2APB破坏。这些蛋白的极化定位和募集导致Ca2+优先进入，这是在顶极开始的。这些发现表明，除了Orai1， STIM1可能调节其他Ca2+可渗透通道，如trpc。这两个通道都有助于[Ca2+]振荡的频率，从而影响关键的细胞功能。
Polarized Ca2+ signals in secretory epithelial cells are determined by compartmentalized localization of Ca2+ signaling proteins at the apical pole. Recently the ER Ca2+ sensor STIM1 and the Orai channels were shown to play a critical role in store-dependent Ca2+ influx. STIM1 also gates the TRPC channels. Here, we asked how cell stimulation affects the localization, recruitment and function of the native proteins in polarized cells. Inhibition of Orai1, STIM1, or deletion of TRPC1 reduces Ca2+ influx and frequency of Ca2+ oscillations. Orai1 localization is restricted to the apical pole of the lateral membrane. Surprisingly, cell stimulation does not lead to robust clustering of native Orai1, as is observed with expressed Orai1. Unexpectedly, cell stimulation causes polarized recruitment of native STIM1 to both the apical and lateral regions, thus to regions with and without Orai1. Accordingly, STIM1 and Orai1 show only 40% co-localization. Consequently, STIM1 shows higher co-localization with the basolateral membrane marker E-cadherin than does Orai1, while Orai1 showed higher co-localization with the tight junction protein ZO1. TRPC1 is expressed in both apical and basolateral regions of the plasma membrane. Co-IP of STIM1/Orai1/IP3Rs/TRPCs is enhanced by cell stimulation and disrupted by 2APB. The polarized localization and recruitment of these proteins results in preferred Ca2+ entry that is initiated at the apical pole. These findings reveal that in addition to Orai1, STIM1 likely regulates other Ca2+ permeable channels, such as the TRPCs. Both channels contribute to the frequency of [Ca2+] oscillations and thus impact critical cellular functions.
登录
查看更多内容
影响因子：
3.5
作者：
Lee KP;Yuan JP;Hong JH;So I;Worley PF;Muallem S
通讯作者：
Muallem S
影响因子：
64.5
作者：
Park CY;Hoover PJ;Mullins FM;Bachhawat P;Covington ED;Raunser S;Walz T;Garcia KC;Dolmetsch RE;Lewis RS
通讯作者：
Lewis RS
影响因子：
4.8
作者：
Ong, Hwei Ling;Cheng, Kwong Tai;Ambudkar, Indu S.
通讯作者：
Ambudkar, Indu S.
DOI：
10.1076/ejom.40.4.203.16691
发表时间：
2002-10-01
期刊：
European Journal of Morphology
影响因子：
--
作者：
Murakami, M.;Yoshimura, K.;Riva, A.
通讯作者：
Riva, A.
影响因子：
4.8
作者：
Kim, Min Seuk;Zeng, Weizhong;Muallem, Shmuel
通讯作者：
Muallem, Shmuel