Inositol hexakisphosphate kinase 3 promotes focal adhesion turnover via interactions with dynein intermediate chain 2

Tomas Rojas, Weiwei Cheng, Zhe Gao, Xiaoqi Liu, Yakun Wang, Adarsha P. Malla, Alfred C. Chin, Lewis Romer, Solomon H Snyder, Chenglai Fu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)3278-3287
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume116
Issue number8
DOIs
Publication statusPublished - Feb 19 2019

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Keywords

  • Cell migration
  • Dynein
  • FAK
  • Focal adhesion
  • IP6K

ASJC Scopus subject areas

  • General

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