LA JOLLA, CA--Among stem cell biologists there are few better-known proteins than nestin, whose very presence in an immature cell identifies it as a "stem cell," such as a neural stem cell. As helpful as this is to researchers, until now no one knew which purpose nestin serves in a cell.
In a study published in the Jan. 30, 2011, advance online edition of Nature Neuroscience, Salk Institute of Biological Studies investigators led by Kuo-Fen Lee, PhD., show that nestin has reason for being in a completely different cell type--muscle tissue. There, it regulates formation of the so-called neuromuscular junction, the contact point between muscle cells and "their" motor neurons.
Knowing this not only deepens our understanding of signaling mechanisms connecting brain to muscle, but could aid future attempts to strengthen those connections in cases of neuromuscular disease or spinal cord injury.
"Nestin was a very well known molecule but no one knew what it did in vivo," says Lee, a professor in the Clayton Foundation Laboratories for Peptide Biology. "Ours is the first study to show that it actually has a physiological function."
Previously, researchers knew that as the neuromuscular junction formed in a developing embryo, so-called positive factors cemented connections between incoming nerve fibers and dense clusters of neurotransmitter receptors facing them on muscle fibers. However, in a 2005 Neuron paper Lee defined a counterbalancing factor--the protein cdk5--that whisked away, or dispersed, superfluous muscle receptors lying outside the contact zone, or synapse, so only the most efficient connections were maintained.
The current study addresses how cdk5, which catalytically adds chemical phosphate groups to target proteins, eliminates useless "extrasynaptic" connections. Reasoning that cdk5 must act by chemically modifying a second protein, Jiefei Yang, PhD., a post-doctoral fellow in the Lee lab and
|Contact: Gina Kirchweger|