title: Cell shape-dependent Control of Ca2+ influx and cell cycle progression in Swiss 3T3 fibroblasts.
abstract: 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 mum 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.
authors: Department of Human Anatomy and Cell Biology, School of Biomedical Sciences, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool L69 3GE, United Kingdom.
authors: Stephen R
authors: SR
authors: Pennington
authors: Brian J
authors: BJ
authors: Foster
authors: Shaun R
authors: SR
authors: Hawley
authors: Rosalind E
authors: RE
authors: Jenkins
authors: Olga
authors: O
authors: Zolle
authors: Michael R H
authors: MR
authors: White
authors: Christine J
authors: CJ
authors: McNamee
authors: Peter
authors: P
authors: Sheterline
authors: Alec W M
authors: AW
authors: Simpson
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002453:Cell Cycle; D048430:Cell Shape; D003599:Cytoskeleton / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D016196:S Phase; D015398:Signal Transduction
chemical_list: D002118:Calcium