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 integrins in cell division remains mostly unexplored. Using two cellular systems, we demonstrate that a point mutation in the beta1 cytoplasmic domain (beta1 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 beta1 tail can regulate centrosome function, the assembly of the mitotic spindle, and cytokinesis.
Reverte
Carlos G
CG
Center for Cell Biology and Cancer Research, Albany Medical College, NY 12208, USA.
Benware
Angela
A
Jones
Christopher W
CW
LaFlamme
Susan E
SE
D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D016466:CHO Cells; D002453:Cell Cycle / Q000502:physiology; D018385:Centrosome / Q000378:metabolism*; D006224:Cricetinae; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D048749:Cytokinesis / Q000502:physiology*; D019012:Integrin beta1 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D007399:Interphase / Q000502:physiology; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000502:physiology; D017354:Point Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D008941:Spindle Apparatus / Q000378:metabolism*
D000906:Antibodies; D019012:Integrin beta1; D019938:Cyclin D1