title: Cell-density-dependent regulation of actin gene expression due to changes in actin treadmilling.
abstract: The actins are essential cytoskeletal proteins required for the survival and growth of cells. The transitions between soluble (G-actin) and filamentous (F-actin) forms of actin (actin treadmilling) are complexly regulated. Here we show that the expression of the cytoplasmic beta-actin and gamma-actin genes is down-regulated in mouse fibroblasts when the cell density of the culture increases. Conversely, a dense culture replated at lower density results in increases in actin mRNA levels within a few hours. Concomitant with these changes in mRNA levels, we observe increased depolymerization of actin microfilaments at higher densities resulting in an elevated G-actin to F-actin ratio. By using actin polymerization inhibitors, we show that the density-dependent change in actin gene expression is dependent on changes in the ratio of G-actin vs. F-actin levels. Therefore, actin treadmilling and actin gene regulation are not coregulated by cell density, but represent a linear signal transduction pathway in which actin treadmilling regulates actin gene transcription. The physiological transition represented by the growth of a sparse fibroblast population into a confluent and growth-arrested population represents a useful model for the study of how the actin treadmill exerts its action on the gene expression program of cells.
authors.affiliation: Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, MA 02115, USA. michel.schmitt-ney@unito.it
authors.forename: Michel
authors.initials: M
authors.lastname: Schmitt-Ney
authors.forename: Joel F
authors.initials: JF
authors.lastname: Habener
mesh_terms: D016475:3T3 Cells / Q000166:cytology; D000199:Actins / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002452:Cell Count; D002455:Cell Division / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology*; D017931:DNA Primers; D051379:Mice
chemical_list: D000199:Actins; D017931:DNA Primers