Perturbing Integrin Function Inhibits Microtubule Growth from Centrosomes, Spindle Assembly, and Cytokinesis

In many mammalian cell types, integrin-mediated cell-matrix adhesion is required for the G1-S transition of the cell cycle. As cells approach mitosis, a dramatic remodeling of their cytoskeleton accompanies dynamic changes in matrix adhesion, suggesting a mechanistic link. However, the role of integ...

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Bibliographic Details
Published in:The Journal of cell biology 2006-08, Vol.174 (4), p.491-497
Main Authors: Carlos G. Reverte, Angela Benware, Jones, Christopher W., LaFlamme, Susan E.
Format: Article
Language:English
Subjects:
Actin Cytoskeleton - metabolism
Animals
Antibodies - pharmacology
Cell cycle
Cell Cycle - physiology
Cell division
Cell growth
Cell lines
Centrosome - metabolism
Centrosomes
CHO Cells
Cricetinae
Cyclin D1 - genetics
Cyclin D1 - metabolism
Cytokines
Cytokinesis
Cytokinesis - physiology
Daughter cells
Integrin beta1 - chemistry
Integrin beta1 - genetics
Integrin beta1 - metabolism
Integrins
Interphase - physiology
Microtubules - metabolism
Mitosis - physiology
Point Mutation - genetics
Protein Structure, Tertiary - genetics
Regrowth
Signal Transduction - physiology
Spindle Apparatus - metabolism
Stem cells
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Summary:In many mammalian cell types, integrin-mediated cell-matrix adhesion is required for the G1-S transition of the cell cycle. As cells approach mitosis, a dramatic remodeling of their cytoskeleton accompanies dynamic changes in matrix adhesion, suggesting a mechanistic link. However, the role of integrins in cell division remains mostly unexplored. Using two cellular systems, we demonstrate that a point mutation in the β1 cytoplasmic domain (β1 tail) known to decrease integrin activity supports entry into mitosis but inhibits the assembly of a radial microtubule array focused at the centrosome during interphase, the formation of a bipolar spindle at mitosis and cytokinesis. These events are restored by externally activating the mutant integrin with specific antibodies. This is the first demonstration that the integrin β1 tail can regulate centrosome function, the assembly of the mitotic spindle, and cytokinesis.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200603069