Chlamydomonas is particularly well suited as an organism to dissect the control mechanisms behind cell size not only because of its simplicity but due to its peculiar cell cycle: during a prolonged growth phase cells enlarge to many times their original size and then suddenly divide several times in rapid succession. Despite this rapid-fire response, cell division is tightly controlled by a sizing mechanism that ensures daughter cells are never too large or too small.
In the course of earlier work, Umen identified an RB homolog encoded by the mat3 gene in C. reinhardtii and later discovered algal counterparts of other players in the RB pathway in humans and mice. To analyze their function in Chlamydomonas, the Salk team isolated cells with mutations in individual members of the RB signaling pathway and things immediately started to go wrong.
Explains Umen, "Cells with mutations in the C. reinhardtii RB homolog start dividing prematurely, and continue dividing excessively, producing abnormally small daughter cells. Mutations in the algal versions of two key targets of the RB tumor suppressor have exactly the opposite effect of RB mutations, resulting in abnormally large cells that don't divide when they should." These findings demonstrate that once cells reach a critical size, they need those two RB target proteins to divide on schedule.
"The interesting thing for us is that the whole genetic module has been conserved from algae to plants to humans," says Umen. "It's been controlling cell division for well over a billion years. As multicellular
Contact: Gina Kirchweger