Journal article
Nck enables directional cell migration through the coordination of polarized membrane protrusion with adhesion dynamics
Journal of cell science, v 126(7), pp 1637-1649
01 Apr 2013
PMID: 23444376
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Directional migration requires the coordination of cytoskeletal changes essential for cell polarization and adhesion turnover. Extracellular signals that alter tyrosine phosphorylation drive directional migration by inducing reorganization of the actin cytoskeleton. It is recognized that Nck is an important link between tyrosine phosphorylation and actin dynamics; however, the role of Nck in cytoskeletal remodeling during directional migration and the underlying molecular mechanisms remain largely undetermined. In this study, a combination of molecular genetics and quantitative live cell microscopy was used to show that Nck is essential in the establishment of front-back polarity and directional migration of endothelial cells. Time-lapse differential interference contrast and total internal reflection fluorescence microscopy showed that Nck couples the formation of polarized membrane protrusions with their stabilization through the assembly and maturation of cell-substratum adhesions. Measurements by atomic force microscopy showed that Nck also modulates integrin alpha 5 beta 1-fibronectin adhesion force and cell stiffness. Fluorescence resonance energy transfer imaging revealed that Nck depletion results in delocalized and increased activity of Cdc42 and Rac. By contrast, the activity of RhoA and myosin II phosphorylation were reduced by Nck knockdown. Thus, this study identifies Nck as a key coordinator of cytoskeletal changes that enable cell polarization and directional migration, which are crucial processes in development and disease.
Metrics
Details
- Title
- Nck enables directional cell migration through the coordination of polarized membrane protrusion with adhesion dynamics
- Creators
- Sankar P. Chaki - Texas A&M UniversityRola Barhoumi - Texas A&M UniversityMatthew E. Berginski - Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USAHarini Sreenivasappa - Texas A&M UniversityAndreea Trache - Texas A&M UniversityShawn M. Gomez - Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27599 USAGonzalo M. Rivera - Texas A&M University
- Publication Details
- Journal of cell science, v 126(7), pp 1637-1649
- Publisher
- Company Biologists Ltd
- Number of pages
- 13
- Grant note
- 0735282N / Scientist Development Grant from the American Heart Association (AHA) Texas AM University 0747334 / National Science Foundation (NSF) CAREER award; National Science Foundation (NSF); NSF - Office of the Director (OD)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Cell Imaging Center
- Web of Science ID
- WOS:000318775400010
- Scopus ID
- 2-s2.0-84877950657
- Other Identifier
- 991022008194004721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Cell Biology