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AKAP6 通过将高尔基复合体和细胞核连接起来，从而调控核包膜微管组织中心，这一过程涉及 AKAP9。

AKAP6 orchestrates the nuclear envelope microtubule-organizing center by linking golgi and nucleus via AKAP9.

机构信息

Experimental Renal and Cardiovascular Research, Department of Nephropathology, Institute of Pathology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Erlangen, Germany.

Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.

出版信息

Elife. 2020 Dec 9;9:e61669. doi: 10.7554/eLife.61669.

DOI:10.7554/eLife.61669
PMID:33295871
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7725499/
Abstract

The switch from centrosomal microtubule-organizing centers (MTOCs) to non-centrosomal MTOCs during differentiation is poorly understood. Here, we identify AKAP6 as key component of the nuclear envelope MTOC. In rat cardiomyocytes, AKAP6 anchors centrosomal proteins to the nuclear envelope through its spectrin repeats, acting as an adaptor between nesprin-1α and Pcnt or AKAP9. In addition, AKAP6 and AKAP9 form a protein platform tethering the Golgi to the nucleus. Both Golgi and nuclear envelope exhibit MTOC activity utilizing either AKAP9, or Pcnt-AKAP9, respectively. AKAP6 is also required for formation and activity of the nuclear envelope MTOC in human osteoclasts. Moreover, ectopic expression of AKAP6 in epithelial cells is sufficient to recruit endogenous centrosomal proteins. Finally, AKAP6 is required for cardiomyocyte hypertrophy and osteoclast bone resorption activity. Collectively, we decipher the MTOC at the nuclear envelope as a bi-layered structure generating two pools of microtubules with AKAP6 as a key organizer.

摘要

从中心体微管组织中心 (MTOC) 到分化过程中非中心体 MTOC 的转变知之甚少。在这里，我们确定 AKAP6 是核膜 MTOC 的关键组成部分。在大鼠心肌细胞中，AKAP6 通过其 spectrin 重复序列将中心体蛋白锚定在核膜上，充当 nesprin-1α 和 Pcnt 或 AKAP9 之间的衔接物。此外，AKAP6 和 AKAP9 形成一个蛋白质平台，将高尔基体与细胞核连接起来。高尔基体和核膜都利用 AKAP9 或 Pcnt-AKAP9 分别发挥 MTOC 活性。AKAP6 对于人类破骨细胞核膜 MTOC 的形成和活性也是必需的。此外，上皮细胞中 AKAP6 的异位表达足以招募内源性中心体蛋白。最后，AKAP6 是心肌细胞肥大和破骨细胞骨吸收活性所必需的。总之，我们揭示核膜上的 MTOC 是一个双层结构，通过 AKAP6 作为关键组织者产生两个微管池。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d87e/7725499/d4de4c50d81d/elife-61669-fig9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d87e/7725499/d4de4c50d81d/elife-61669-fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d87e/7725499/c00206d14760/elife-61669-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d87e/7725499/96f9fcbd6a27/elife-61669-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d87e/7725499/9f462ed1a62a/elife-61669-fig1-figsupp2.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d87e/7725499/db4726722f60/elife-61669-fig6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d87e/7725499/7737316ebace/elife-61669-fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d87e/7725499/5c47b68c9a9b/elife-61669-fig7-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d87e/7725499/c48db8ca81e7/elife-61669-fig8.jpg
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