Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics.

Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics.
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DOI:
10.1083/jcb.200204081
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发表时间:
2002-08-19
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Scott JD
Scott JD
中科院分区:
其他
文献类型:
--
作者:
Alto NM;Soderling J;Scott JD

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A-激酶锚定蛋白(AKAP)将cAMP依赖性蛋白激酶(PKA)和其他信号传导酶拴系到不同的亚细胞器。使用酵母双杂交的方法,我们证明Rab 32,小分子量G蛋白的Ras超家族的成员,直接与PKA的II型调节亚基相互作用。细胞和生物化学研究证实Rab 32在细胞内作为AKAP发挥作用。PKA的保守决定簇已被定位于所有Rab家族成员共有的保守α5螺旋内的位点。亚细胞分级分离和免疫荧光方法表明Rab 32和一部分细胞PKA库与线粒体相关。Rab 32的GTP结合缺陷突变体的瞬时转染促进线粒体在微管组织中心的异常积累。对该突变体的进一步分析表明,微管细胞骨架的破坏导致线粒体异常伸长。这暗示Rab 32是线粒体分裂同步化的参与者。因此,Rab 32是参与PKA的线粒体锚定和线粒体动力学的双重功能蛋白。
A-kinase anchoring proteins (AKAPs) tether the cAMP-dependent protein kinase (PKA) and other signaling enzymes to distinct subcellular organelles. Using the yeast two-hybrid approach, we demonstrate that Rab32, a member of the Ras superfamily of small molecular weight G-proteins, interacts directly with the type II regulatory subunit of PKA. Cellular and biochemical studies confirm that Rab32 functions as an AKAP inside cells. Anchoring determinants for PKA have been mapped to sites within the conserved α5 helix that is common to all Rab family members. Subcellular fractionation and immunofluorescent approaches indicate that Rab32 and a proportion of the cellular PKA pool are associated with mitochondria. Transient transfection of a GTP binding–deficient mutant of Rab32 promotes aberrant accumulation of mitochondria at the microtubule organizing center. Further analysis of this mutant indicates that disruption of the microtubule cytoskeleton results in aberrantly elongated mitochondria. This implicates Rab32 as a participant in synchronization of mitochondrial fission. Thus, Rab32 is a dual function protein that participates in both mitochondrial anchoring of PKA and mitochondrial dynamics.
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