Identification of KRAP-expressing cells and the functional relevance of KRAP to the subcellular localization of IP3R in the stomach and kidney.
Identification of KRAP-expressing cells and the functional relevance of KRAP to the subcellular localization of IP3R in the stomach and kidney.
复制标题
DOI：
10.3892/ijmm.2012.1126
复制
发表时间：
2012-12
影响因子：
5.4
通讯作者：
Shirasawa S
中科院分区：
文献类型：
--
作者：
Fujimoto T;Shirasawa S
KRAS 诱导的肌动蛋白相互作用蛋白 (KRAP) 最初被确定为结直肠癌中表达失调的基因之一，在生理条件下参与全身能量稳态和外分泌系统的调节。我们最近发现 KRAP 是一种与肌醇 1,4,5-三磷酸受体 (IP3R) 相关的分子，对于 IP3R 在肝脏和胰腺中的正确亚细胞定位至关重要。然而，KRAP 的表达及其在其他组织中的精确功能仍然难以捉摸。在这项研究中，我们的目的是鉴定小鼠胃和肾脏中表达 KRAP 的细胞，并检查 KRAP 表达在这些组织中 IP3R 定位调节中的相关性。在胃中，KRAP和IP3R的双重免疫组织化学染色表明KRAP在粘液细胞和主细胞的顶端区域表达，并且IP3R3在这些细胞中主要与KRAP共定位。此外，IP3R2 还与 IP3R3 在主细胞中共定位。值得注意的是，在 KRAP 缺陷小鼠中，IP3R3 和 IP3R2 在主细胞中的正确定位以及 IP3R3 在粘液细胞中的正确定位被显着消除。在肾脏中，KRAP 在近端肾小管细胞的顶端和基底区域表达。有趣的是，KRAP 缺陷消除了 IP3R1 在近端肾小管细胞中的定位。最后，胃和肾脏的免疫共沉淀研究验证了 KRAP 与 IP3R 的物理关联。这些发现表明，KRAP 与 IP3R 物理结合，并调节 IP3R 在粘液细胞和胃主细胞以及肾脏近端肾小管细胞中的正确定位。
KRAS-induced actin-interacting protein (KRAP), originally identified as one of the deregulated genes expressed in colorectal cancer, participates under physiological conditions in the regulation of systemic energy homeostasis and of the exocrine system. We have recently found that KRAP is a molecule associated with inositol 1,4,5-trisphosphate receptor (IP3R) and is critical for the proper subcellular localization of IP3R in the liver and the pancreas. However, the expression of KRAP and its precise function in other tissues remain elusive. In this study, we aimed to identify the KRAP-expressing cells in mouse stomach and kidneys and to examine the relevance of KRAP expression in the regulation of IP3R localization in these tissues. In the stomach, double immunohistochemical staining for KRAP and IP3R demonstrated that KRAP was expressed along with the apical regions in the mucous cells and the chief cells, and IP3R3 was dominantly co-localized with KRAP in these cells. Furthermore, IP3R2 was also co-localized with IP3R3 in the chief cells. It is of note that the proper localization of IP3R3 and IP3R2 in the chief cells and of IP3R3 in the mucous cells were significantly abrogated in KRAP-deficient mice. In the kidneys, KRAP was expressed in both the apical and the basal regions of the proximal tubular cells. Intriguingly, KRAP deficiency abrogated the localization of IP3R1 in the proximal tubular cells. Finally, co-immunoprecipitation study in the stomachs and the kidneys validated the physical association of KRAP with IP3Rs. These findings demonstrate that KRAP physically associates with IP3Rs and regulates the proper localization of IP3Rs in the mucous cells and the chief cells of the stomach and in the proximal tubular cells of the kidneys.
登录
查看更多内容
影响因子：
4.8
作者：
Mills, JC;Andersson, N;Gordon, JI
通讯作者：
Gordon, JI
影响因子：
3.5
作者：
SUGIYAMA, T;YAMAMOTOHINO, M;HASEGAWA, M
通讯作者：
HASEGAWA, M
DOI：
10.1083/jcb.200708200
发表时间：
2007-12-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
deSouza N;Cui J;Dura M;McDonald TV;Marks AR
通讯作者：
Marks AR
影响因子：
2.5
作者：
Husain S;Thrower E
通讯作者：
Thrower E
影响因子：
4.4
作者：
Zhang, Songbai;Fritz, Nicolas;Ibarra, Cristian;Uhlen, Per
通讯作者：
Uhlen, Per