Title | Inositol hexakisphosphate kinase 3 promotes focal adhesion turnover via interactions with dynein intermediate chain 2. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Rojas T, Cheng W, Gao Z, Liu X, Wang Y, Malla AP, Chin AC, Romer LH, Snyder SH, Fu C |
Journal | Proc Natl Acad Sci U S A |
Volume | 116 |
Issue | 8 |
Pagination | 3278-3287 |
Date Published | 2019 02 19 |
ISSN | 1091-6490 |
Keywords | Brain, Cell Adhesion, Cell Movement, Cellular Microenvironment, Cytoplasmic Dyneins, Dendrites, Focal Adhesions, HEK293 Cells, Humans, Neurons, Phosphotransferases (Phosphate Group Acceptor) |
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. |
DOI | 10.1073/pnas.1817001116 |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 30718399 |
PubMed Central ID | PMC6386689 |
Grant List | R01 MH018501 / MH / NIMH NIH HHS / United States R37 MH018501 / MH / NIMH NIH HHS / United States |
Submitted by api_import on December 20, 2019 - 3:23pm