Extracellular control of cell size

Abstract

Both cell growth (cell mass increase) and progression through the cell division cycle are required for sustained cell proliferation. Proliferating cells in culture tend to double in mass before each division, but it is not known how growth and division rates are co-ordinated to ensure that cell size is maintained. The prevailing view is that coordination is achieved because cell growth is rate-limiting for cell-cycle progression. Here, we challenge this view. We have investigated the relationship between cell growth and cell-cycle progression in purified rat Schwann cells, using two extracellular signal proteins that are known to influence these cells. We find that glial growth factor (GGF) can stimulate cell-cycle progression without promoting cell growth. We have used this restricted action of GGF to show that, for cultured Schwann cells, cell growth rate alone does not determine the rate of cell-cycle progression and that cell size at division is variable and depends on the concentrations of extracellular signal proteins that stimulate cell-cycle progression, cell growth, or both.

Ubc9 Regulates Mitosis and Cell Survival during Zebrafish Development

“…In addition, increased cell size might be due to alterations in external signals that dictate growth rates independently of cell cycle progression. It has previously been shown in cell culture systems that growth factor stimulation can lead to cell growth (volume increase), whereas cell cycle progression is blocked (Conlon et al, 2001;Dolznig et al, 2004). A scenario like this might explain the results obtained in our chimerae analyses, where ubc9.1 morphant chondrocytes showed a less pronounced size phenotype when exposed to a wild-type environment.…”

Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression

“…Rather, cell size is dynamic and responsive to the extracellular milieu. Indeed, budding yeast grown on poor carbon sources proliferate at reduced cell size (Flick et al, 1998), and rat Schwann cells divide at a size that varies depending on the concentration of extracellular growth factors in the media (Conlon et al, 2001). It is intriguing that the same set of mTOR-dependent downstream effectors that regulate cell growth and cell size, S6K1, 4E-BP1, and eIF4E, also regulate the rate of cell cycle progression: When quiescent U2OS cells are stimulated with serum to enter G 1 phase from G 0 , overexpression of S6K1 and eIF4E accelerates S phase entry, while reduced expression of S6K1 with RNAi or overexpression of a dominant mutant of 4E-BP1 inhibits the rate of S phase entry (Fingar et al, 2004).…”

Molecular mechanism of size control in development and human diseases

“…In an attempt to examine how cell growth and cell division are coordinated in order to keep a constant cell size, Conlon et al [161] examined cell growth and cell division after treatment of rat Schwann cells with glial growth factor (GGF). They found that GGF can stimulate cell cycle progression without promoting cell growth, further confirming studies in yeast and Drosophila that proliferation can not drive cell growth.…”