Nuclear Localization of Integrin Cytoplasmic Domain-associated Protein-1 (ICAP1) Influences β1 Integrin Activation and Recruits Krev/Interaction Trapped-1 (KRIT1) to the Nucleus
| Autor: | David A. Calderwood, Clotilde Huet-Calderwood, Kyle M. Draheim, Bertrand Simon |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Integrin Population Active Transport Cell Nucleus CHO Cells medicine.disease_cause Biochemistry CD49c 03 medical and health sciences Cricetulus 0302 clinical medicine Cricetinae Proto-Oncogene Proteins Protein targeting medicine Animals Humans education KRIT1 Protein Molecular Biology Adaptor Proteins Signal Transducing Cell Nucleus education.field_of_study biology Chemistry Integrin beta1 Intracellular Signaling Peptides and Proteins Membrane Proteins Cell Biology Cell biology Cell nucleus HEK293 Cells 030104 developmental biology medicine.anatomical_structure Integrin alpha M biology.protein Integrin beta 6 Microtubule-Associated Proteins 030217 neurology & neurosurgery Nuclear localization sequence Signal Transduction |
| Zdroj: | Journal of Biological Chemistry. 292:1884-1898 |
| ISSN: | 0021-9258 |
| Popis: | Binding of ICAP1 (integrin cytoplasmic domain-associated protein-1) to the cytoplasmic tails of β1 integrins inhibits integrin activation. ICAP1 also binds to KRIT1 (Krev interaction trapped-1), a protein whose loss of function leads to cerebral cavernous malformation, a cerebrovascular dysplasia occurring in up to 0.5% of the population. We previously showed that KRIT1 functions as a switch for β1 integrin activation by antagonizing ICAP1-mediated inhibition of integrin activation. Here we use overexpression studies, mutagenesis, and flow cytometry to show that ICAP1 contains a functional nuclear localization signal and that nuclear localization impairs the ability of ICAP1 to suppress integrin activation. Moreover, we find that ICAP1 drives the nuclear localization of KRIT1 in a manner dependent upon a direct ICAP1/KRIT1 interaction. Thus, nuclear-cytoplasmic shuttling of ICAP1 influences both integrin activation and KRIT1 localization, presumably impacting nuclear functions of KRIT1. |
| Databáze: | OpenAIRE |
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