Proteins have to be transported through the complex internal environment of a cell to reach their site of function. Nowhere is this more evident than in brain cells, or neurons, which communicate with each other over long distances at specialized sites of contact, called synapses. Through a poorly understood process, the neuron must sort through thousands of protein to identify a small set of proteins that must travel to the synapse. These proteins are then packaged into membrane packages, called vesicles, that are transported along the cellular cytoskeleton by motor proteins, just like buses on a highway. In some cases the proteins must travel as much as 1-meter to reach the synapse, comparable to a person traveling 60,000 miles just to get to work!
Schizophrenia is a devastating mental disorder characterized by visual and auditory hallucinations, paranoid delusions, and disorganized speech and thought. In the December 15, 2011 issue of the journal Molecular Biology of the Cell, Victor Faundez and colleagues report that dysbindin, a protein implicated as a risk factor for schizophrenia, is required for the sorting of specific proteins into vesicles bound for the synapse. In other words, defects in dysbindin function cause a set of proteins to miss their “bus” to the synapse! This new insight has profound implications for the treatment of schizophrenia and suggests that targeting the function of specific proteins at the synapse, as many current therapies do, may be the wrong approach. Instead, getting the right proteins back on the “bus” to the synapse might be the vehicle to success.
Larimore, J., Tornieri, K., Ryder, P.V., Gokhale, A., Zlatic, S.A., Craige, B., Lee, J.D., Talbot, K., Pare, J.F., Smith, Y., and Faundez, V. (2011) The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse. Mol Biol Cell, 22(24) 4854-4867.