Sunday, 17 May 2015

On being the right (cell) size

Miriam B. Ginzberg, Ran Kafri, and Marc Kirschner

Across tissues, cell size is highly variable: pancreatic beta cells have a characteristic length of ~10um whereas adipocytes are ~80um. Despite this inter-tissue diversity, within individual tissues, cell size is much more homogeneous. This review discusses mechanisms to explain this homogeneity.

In order for a population of cells to control their size, cells can either vary the amount of time they spend growing, or the rate at which they grow. The authors discuss evidence supporting the former hypothesis, that cells vary the amount of time they spend in G1 phase, such that cells only progress to S phase of the cell cycle once they reach a particular target size. One possibility for how this may be achieved mechanistically is the diffusion of intracellular 'ruler' proteins, whose concentration gradient can be used to measure distance.

The reason why cells have a tight control over their size is not completely clear. A 1945 study by Fankhauser in polyploid salamander larvae showed that normal structures could be formed even with large alterations in cell size, across many (but not all) cell types. A notable exception to this is the brain, where cell size affects its morphological complexity.

Perhaps a mitochondrial perspective may aid in the explanation of some of these observations? It is known that inheritance of mitochondrial content correlates with global transcription rate (see here and here). Furthermore, there is evidence to suggest that mitochondrial replication occurs in G1 phase, coinciding with the cell size checkpoint. Perhaps there exists some mitochondrial set point before progression is allowed to S-phase, with a corresponding global transcription rate and characteristic cell size?

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