How to map cell-signaling molecules to their targets
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A team of University of Montreal and 平特五不中 researchers have devised a method to identify how signaling molecules orchestrate the sequential steps in cell division. In an article published online today in the Proceedings of the National Academy of Sciences, the scientists explain how they could track the relationship between signaling molecules and their target molecules to establish where, when and how the targets are deployed to perform the many steps necessary to replicate an individual cell鈥檚 genome and surrounding structures.
Breakdowns in individual steps in these processes are a hallmark of a number of diseases, including cancers. The method outlined in the PNAS paper could provide a valuable tool to researchers seeking to better understand these processes.
鈥淗ow living cells divide and how this process is accurately achieved are among the deepest questions scientists have been addressing for decades,鈥 said Dr. Stephen Michnick, co-senior investigator and a University of Montreal biochemistry professor.听 Co-senior investigator Jackie Vogel, a biology professor at 平特五不中, said, 鈥淲e know what are the main players in cell division 鈥 molecules called cyclins and a common actuator molecule called Cdk1 鈥 but it has proved a vexing problem to figure out precisely how the cyclin-Cdk1 partners deploy target molecules to orchestrate everything that must happen and in precisely the right order to assure accurate cell division.鈥澨
The University of Montreal and 平特五不中 team worked out a method to identify interactions between cyclin-Cdk1 (cyclin-dependent kinase 1) complexes and their targets in living cells.听 Cdk1 is a signaling protein that plays a key role in cell division 鈥 it has been studied extensively in yeast, because of yeast鈥檚 rapid reproduction, and is found in many other living organisms including humans. 鈥淚t is a simple method that could be performed in any laboratory, unlike existing methods that are much more labor- and skill-intensive,鈥 said Dr. Michnick.
鈥淭he method also picks up cyclin-Cdk1 interactions that traditional methods don鈥檛,鈥 added Dr. Vogel. 鈥淔or instance, we study the assembly of a massive molecular machine called the mitotic spindle, a structure that orchestrates the coordinated separation of two copies of the genome between the two new cells that emerge from division. We鈥檇 been chasing, for over a decade, an elusive link between a specific cyclin called Clb3-Cdk1 complex and a spindle target called gamma-tubulin that we thought could be a key step in building mitotic spindles accurately. All evidence pointed to this interaction, including a massive effort I was involved in to map out cellular communication directed to the centrosome, a molecular machine that organizes assembly of the mitotic spindle. So we teamed up with Dr. Michnick to try the new method and out popped the Clb3-Cdk1-gamma tubulin interaction -- just like that.鈥澨 Now, in collaboration with Paul Fran莽ois, a physics professor at 平特五不中, the researchers have been able to use this information to show that the Clb3-Cdk1-gamma-tubulin interaction controls a massive remodeling of the mitotic spindle.
鈥淭he tool that we鈥檝e developed will be available to the scientific community and concerted efforts by many labs may ultimately unlock the mysteries of one of life鈥檚 most essential processes,鈥 said Dr. Michnick.
IMAGE: A mitotic spindle hub (the orange and grey hub-and-spoke structure) primed by Cdk-Clb3 signaling (red). CREDIT:听 Conrad Hall, 平特五不中
Notes:
The University of Montreal is known officially as Universit茅 de Montr茅al. The research involved in the study 鈥淒issection of Cdk1鈥揷yclin complexes in vivo鈥 was financed by Canadian Institutes of Health Research (CIHR) grants MOP-GMX-192838 and MOP-GMX- 231013 to Dr. Michnick and CIHR grant MOP-123335 and听 Natural Sciences and Engineering Research Council (Canada) grant RGPIN 262246 to Dr. Vogel. This press release references findings by Keck et al., Science 2011 and Nazarova et al. Molecular Biology of the Cell, 2013.
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