BMP2K phosphorylates AP-2 and regulates clathrin-mediated endocytosis.

IF 3.6 3区 生物学 Q3 CELL BIOLOGY Traffic Pub Date : 2021-11-01 Epub Date: 2021-09-27 DOI:10.1111/tra.12814
Shikha T Ramesh, Kolaparamba V Navyasree, Sneha Sah, Anjitha B Ashok, Nishada Qathoon, Suryasikha Mohanty, Rajeeb K Swain, Perunthottathu K Umasankar
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引用次数: 7

Abstract

Phosphorylation of the central adaptor protein complex, AP-2 is pivotal for clathrin-mediated endocytosis (CME). Here, we uncover the role of an uncharacterized kinase (BMP-2 inducible kinase-BMP2K) in AP-2 phosphorylation. We demonstrate that BMP2K can phosphorylate AP-2 in vitro and in vivo. Functional impairment of BMP2K impedes AP-2 phosphorylation leading to defects in clathrin-coated pit (CCP) morphology and cargo internalization. BMP2K engages AP-2 via its extended C-terminus and this interaction is important for its CCP localization and function. Notably, endogenous BMP2K levels decline upon functional impairment of AP-2 indicating AP-2 dependent BMP2K stabilization in cells. Further, functional inactivation of BMP2K in zebrafish embryos yields gastrulation phenotypes which mirror AP-2 loss-of-function suggesting physiological relevance of BMP2K in vertebrates. Together, our findings propose involvement of a novel kinase in AP-2 phosphorylation and in the operation of CME.

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BMP2K磷酸化AP-2并调节网格蛋白介导的内吞作用。
中心接头蛋白复合物AP-2的磷酸化是网格蛋白介导的内吞作用(CME)的关键。在这里,我们揭示了一种未表征的激酶(BMP-2诱导激酶- bmp2k)在AP-2磷酸化中的作用。我们证明BMP2K可以在体外和体内磷酸化AP-2。BMP2K的功能障碍阻碍AP-2磷酸化,导致网格蛋白包覆坑(CCP)形态和货物内化缺陷。BMP2K通过其扩展的c端与AP-2结合,这种相互作用对其CCP定位和功能很重要。值得注意的是,内源性BMP2K水平在AP-2功能损伤时下降,表明细胞中AP-2依赖性BMP2K稳定。此外,斑马鱼胚胎中BMP2K的功能失活产生的原肠胚表型反映了AP-2的功能丧失,这表明BMP2K在脊椎动物中的生理相关性。总之,我们的研究结果提出了一种新的激酶参与AP-2磷酸化和CME的操作。
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来源期刊
Traffic
Traffic 生物-细胞生物学
CiteScore
8.10
自引率
2.20%
发文量
50
审稿时长
2 months
期刊介绍: Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.
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