肌球蛋白中间链 2 通过与肌醇六磷酸激酶 3 相互作用促进黏着斑转化。
Inositol hexakisphosphate kinase 3 promotes focal adhesion turnover via interactions with dynein intermediate chain 2.
机构信息
Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Division of Neuropathology, Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205.
出版信息
Proc Natl Acad Sci U S A. 2019 Feb 19;116(8):3278-3287. doi: 10.1073/pnas.1817001116. Epub 2019 Feb 4.
Abstract
Cells express a family of three inositol hexakisphosphate kinases (IP6Ks). Although sharing the same enzymatic activity, individual IP6Ks mediate different cellular processes. Here we report that IP6K3 is enriched at the leading edge of migrating cells where it associates with dynein intermediate chain 2 (DIC2). Using immunofluorescence microscopy and total internal reflection fluorescence microscopy, we found that DIC2 and IP6K3 are recruited interdependently to the leading edge of migrating cells, where they function coordinately to enhance the turnover of focal adhesions. Deletion of IP6K3 causes defects in cell motility and neuronal dendritic growth, eventually leading to brain malformations. Our results reveal a mechanism whereby IP6K3 functions in coordination with DIC2 in a confined intracellular microenvironment to promote focal adhesion turnover.
摘要
细胞表达一族三种肌醇六磷酸激酶 (IP6Ks)。尽管具有相同的酶活性，但单个 IP6K 介导不同的细胞过程。在这里，我们报告 IP6K3 在迁移细胞的前缘富集，在那里它与中间链二聚体 2 (DIC2) 相关联。使用免疫荧光显微镜和全内反射荧光显微镜，我们发现 DIC2 和 IP6K3 被招募到迁移细胞的前缘，它们在那里协调作用以增强焦点粘附的周转率。IP6K3 的缺失导致细胞运动和神经元树突生长缺陷，最终导致大脑畸形。我们的结果揭示了一种机制，即 IP6K3 与 DIC2 在受限的细胞内微环境中协调作用，以促进焦点附着的周转率。
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