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About SickKids

November 5, 2007

A New Understanding of the Role of Proteins in Accurate Cell Division

Researchers at SickKids have discovered the role that the mammalian protein Sept 2 plays in cell division, an important breakthrough since failures in the process can lead to cancer. These findings are published in the November 2007 issue of Developmental Cell.

PhD students Emily Joo and Mark Surka, together with SickKids Senior Scientist, Cell Biology Program Head, Dr. William Trimble examined the role of mammalian septins in cytokinesis, the process that divides the nucleus, cytoplasm, organelles, and membranes of a cell into two daughter cells. The accurate control of this process is essential to ensure that each cell receives the correct genetic composition, thereby preventing cell mutation or cell death.

The mammalian septin called Sept 2 belongs to a family of enzymes, known as GTPases that are associated with actin stress fibres, part of the cytoskeleton of interphase (non-dividing) cells and the contractile ring in dividing cells. The team found that Sept 2 binds directly to non-muscle myosin IIA and serves as a molecular platform to facilitate the interaction of myosin II and its kinases (enzymes). In so doing, it ensures the full activation of myosin II that is necessary for the final stages of cytokinesis. In the absence of this scaffolding activity, myosin is not efficiently phosphorylated, which leads to the loss of stress fibres and cytokinesis failures.

The team’s findings revealed unexpected links between septins and myosin regulation and offer important new insights into myosin activity and function, applicable to a variety of cellular functions beyond cell division. In the future, researchers may examine whether this relationship holds true in other myosin-dependent functions such as cell migration, which is implicated in inflammation, a key component of chronic diseases such as arthritis.

The research was supported by the Canadian Cancer Society and the Canadian Institutes of Health Research.

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The Hospital for Sick Children