AKAP350 Is involved in the development of apical "canalicular" structures in hepatic cells HepG2.
AKAP350 Is involved in the development of apical "canalicular" structures in hepatic cells HepG2.
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DOI：
10.1002/jcp.22713
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发表时间：
2012-01
影响因子：
5.6
通讯作者：
Larocca, Maria C.
中科院分区：
文献类型：
--
作者：
Mattaloni, Stella M.;Kolobova, Elena;Favre, Cristian;Marinelli, Raul A.;Goldenring, James R.;Larocca, Maria C.
肝细胞是上皮细胞，其顶极构成胆小管。小管极的建立和维持是一个精细调节的过程，决定了初级胆汁分泌的效率。蛋白激酶A（PKA）在不同水平上调节这一过程。AKAP 350是一种A-激酶锚定蛋白，其支架蛋白复合物参与调节高尔基体和微管细胞骨架的动态结构，促进微管在该细胞器处成核。在这项研究中，我们评估了AKAP 350是否参与肝细胞衍生的HepG 2细胞中胆管样结构的发育。我们发现AKAP 350在HepG 2细胞中将PKA募集到中心体和高尔基体。AKAP 350从这些细胞器中的去定位导致顶端细胞极化降低。AKAP 350表达的减少抑制了小管结构的形成，并损害了小管极处的F-肌动蛋白组织。此外，AKAP 350表达的缺失导致顶端小管膜上p-糖蛋白（MDR 1/ABCB 1）的极化表达减少。AKAP 350敲低对小管结构形成和肌动蛋白组织的影响可以通过消耗CLIP相关蛋白（CLASP）抑制高尔基体微管成核来模拟。我们的数据显示，AKAP 350参与的机制，确定小管结构的发展，以及准确的小管表达不同的蛋白质和肌动蛋白组织，并提供证据的高尔基体微管成核参与肝细胞顶端极化。
Hepatocytes are epithelial cells whose apical poles constitute the bile canaliculi. The establishment and maintenance of canalicular poles is a finely regulated process that dictates the efficiency of primary bile secretion. Protein kinase A (PKA) modulates this process at different levels. AKAP350 is an A-kinase anchoring protein that scaffolds protein complexes involved in modulating the dynamic structures of the Golgi apparatus and microtubule cytoskeleton, facilitating microtubule nucleation at this organelle. In this study, we evaluated whether AKAP350 is involved in the development of bile canaliculi-like structures in hepatocyte derived HepG2 cells. We found that AKAP350 recruits PKA to the centrosomes and Golgi apparatus in HepG2 cells. De-localization of AKAP350 from these organelles led to reduced apical cell polarization. A decrease in AKAP350 expression inhibited the formation of canalicular structures and impaired F-actin organization at canalicular poles. Furthermore, loss of AKAP350 expression led to diminished polarized expression of the p-glycoprotein (MDR1/ABCB1) at the apical “canalicular” membrane. AKAP350 knock down effects on canalicular structures formation and actin organization could be mimicked by inhibition of Golgi microtubule nucleation by depletion of CLIP associated proteins (CLASPs). Our data reveal that AKAP350 participates in mechanisms which determine the development of canalicular structures as well as accurate canalicular expression of distinct proteins and actin organization, and provide evidence on the involvement of Golgi microtubule nucleation in hepatocyte apical polarization.
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DOI：
10.1083/jcb.200405094
发表时间：
2005-01-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Mimori-Kiyosue Y;Grigoriev I;Lansbergen G;Sasaki H;Matsui C;Severin F;Galjart N;Grosveld F;Vorobjev I;Tsukita S;Akhmanova A
通讯作者：
Akhmanova A
影响因子：
2.1
作者：
Nishimura, T;Takahashi, M;Ono, Y
通讯作者：
Ono, Y
影响因子：
--
作者：
Berryman, MA;Goldenring, JR
通讯作者：
Goldenring, JR
影响因子：
11.8
作者：
Deng, Manqi;Suraneni, Praveen;Li, Rong
通讯作者：
Li, Rong
影响因子：
30.8
作者：
Kikuchi, S;Hata, M;Tsukita, S
通讯作者：
Tsukita, S