Cells typically contain a cytoskeleton, which helps shuttle things around and provides structural integrity, among other functions. Microtubules are important parts of the cytoskeleton, and new research has shown that they also play a crucial role in ensuring that the signals that cells receive end up in the right places. The findings, which identified a specific protein domain that is critical to this process, have been reported in Cell.
Many vital signals are sent from one cell to another, and when a molecular message is received, signaling proteins outside and inside of the cell respond. For example, molecules like hormones, neurotransmitters, or cytokines might be sent from one cell to another, and get received by a receptor. This can usually trigger a variety of different reactions in the recipient cell, depending on the cell type and the signal. This study has shown that microtubules play a very important part in transmitting these signals. Since microtubules can constantly change by reducing or extending to break or form connections, a signal that is received by a cell can also be moved throughout the interior of a cell to wherever it needs to go by microtubules.
This study focused on a signaling protein known as guanine nucleotide exchange factor H1 (GEFH1); it activates the RhoA signaling pathway, which is related to cell motility and division. When GEFH1 gets to the microtubules of a cell, it can hang onto them, and become deactivated. When the microtubule eventually unravels as part of its normal function, the GEFH1 protein is released. GEFH1 is then activated again, and it triggers the RhoA signaling pathway, starting another cascade of processes.
These findings have provided new insights into fundamental mechanisms of the cell, and showed that the C1 domain of GEFH1 is vital to how the protein links to microtubules.
"They complete our picture of the signaling cascades triggered in the cell by messenger substances such as hormones and cytokines," said senior study author Michel Steinmetz, of the Paul Scherrer Institute (PSI) Center for Life Sciences. "As an active element in this mechanism, microtubules assume an even greater significance."
The study authors noted that this process could also be common to many other signaling molecules and pathways. It may also be possible to manipulate microtubules or the C1 domain in molecules that are shuttled on microtubules for therapeutic purposes.
Sources: Paul Scherrer Institute, Cell
