Cell Shape-dependent Control of Ca2+ Influx and Cell Cycle Progression in Swiss 3T3 Fibroblasts

The ability of adherent cells such as fibroblasts to enter the cell cycle and progress to S phase is strictly dependent on the extent to which individual cells can attach to and spread on a substratum. Here we have used microengineered adhesive islands of 22 and 45 μm diameter surrounded by a nonadh...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-11, Vol.282 (44), p.32112-32120
Main Authors: Pennington, Stephen R., Foster, Brian J., Hawley, Shaun R., Jenkins, Rosalind E., Zolle, Olga, White, Michael R.H., McNamee, Christine J., Sheterline, Peter, Simpson, Alec W.M.
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Calcium - metabolism
Cell Cycle
Cell Shape
Cytoskeleton - metabolism
Fibroblasts - cytology
Fibroblasts - metabolism
Mice
S Phase
Signal Transduction
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Summary:The ability of adherent cells such as fibroblasts to enter the cell cycle and progress to S phase is strictly dependent on the extent to which individual cells can attach to and spread on a substratum. Here we have used microengineered adhesive islands of 22 and 45 μm diameter surrounded by a nonadhesive substratum of polyhydroxyl methacrylate to accurately control the extent to which individual Swiss 3T3 fibroblasts may spread. The effect of cell shape on mitogen-evoked Ca2+ signaling events that accompany entry into the cell cycle was investigated. In unrestricted cells, the mitogens bombesin and fetal calf serum evoked a typical biphasic change in the cytoplasmic free Ca2+ concentration. However, when the spreading of individual cells was restricted, such that progression to S phase was substantially reduced, both bombesin and fetal calf serum caused a rapid transient rise in the cytoplasmic free Ca2+ concentration but failed to elicit the normal sustained influx of Ca2+ that follows Ca2+ release. As expected, restricting cell spreading led to the loss of actin stress fibers and the formation of a ring of cortical actin. Restricting cell shape did not appear to influence mitogen-receptor interactions, nor did it influence the presence of focal adhesions. Because Ca2+ signaling is an essential component of mitogen responses, these findings implicate Ca2+ influx as a necessary component of cell shape-dependent control of the cell cycle.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M705067200