期刊
JOURNAL OF CELL SCIENCE
卷 124, 期 15, 页码 2529-2538出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/jcs.083634
关键词
Protein 4.1R; IQGAP1; Cell migration
类别
资金
- Ministerio de Ciencia e Innovacion (MICINN), Spain
- MICINN [BFU2008-02460, BFU2009-07886, CONSOLIDER COAT CSD2009-00016, SAF-2008-01936]
- Comunidad de Madrid [S-GEN-0166/2006]
In red blood cells, multifunctional protein 4.1R stabilizes the spectrin-actin network and anchors it to the plasma membrane. To contribute to the characterization of functional roles of 4.1R in nonerythroid cells, we have analyzed the participation of protein 4.1R in cell migration. The distribution of endogenous 4.1R is polarized towards the leading edge of migrating cells. Exogenous 4.1R isoforms containing a complete membrane-binding domain consistently localized to plasma membrane extensions enriched in F-actin. Silencing of 4.1R caused the loss of persistence of migration in subconfluent cells and of directional migration in cells moving into a wound. Coimmunoprecipitation and pull-down assays identified the scaffold protein IQGAP1 as a partner for protein 4.1R and showed that the 4.1R membrane-binding domain is involved in binding IQGAP1. Importantly, we show that protein 4.1R is necessary for the localization of IQGAP1 to the leading edge of cells migrating into a wound, whereas IQGAP1 is not required for protein 4.1R localization. Collectively, our results indicate a crucial role for protein 4.1R in cell migration and in the recruitment of the scaffold protein IQGAP1 to the cell front.
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