 elucidate the function of ?-SG in the synaptic transmission. We further hypothesize that ?-SG interacts with other proteins and loss of ?-SG leads to the reduction of the complex at the synapse. The reduction of the complex leads to altered synaptic transmission and plasticity at circuit level, and myoclonus, motor deficits indicative of dystonia, or both, at system level. The rationale for the proposed research is that once the roles of SGCE in causing dysfunction of movement control in the brain are determined, possible interventions to correct M-D can be developed. We are particularly well prepared to undertake the proposed research because we have created a line of Sgce mutant mice that mimic the DYT11 patients. Furthermore, we have developed other genetic and antibody tools that can critically test the above hypothesis. Our other strength is the multidisciplinary approaches we are able to use, which include molecular, genetic, anatomical, biochemical, neurophysiologic, and behavioral techniques. The work will be conducted in a research environment with many NIH-funded investigators and shared NIH-funded core resources that are focused on using animal models of neurological disorders. We plan to test our hypothesis with the following Specific Aims: Specific Aim 1: To identify the interacting proteins, we will prepare the synaptosomal fractions from WT and Sgce KO mouse brains. Immunoprecipitation of the ?-SG complex will be performed using specific monoclonal antibody against ?-SG followed by separation of these proteins by gel electrophoresis. The bands only appeared in the WT mouse brain samples should be ?-SG and the interacting proteins and the bands appears in the Sgce KO mouse brain samples should be false positive bands that non-specifically precipitated in the immunoprecipitation experiment. Protein bands will be isolated and sequenced by Mass Spectrometry. Specific Aim 2: To analyze the effect of loss of ?-SG on the expression levels of the interacting proteins, we will prepare synaptosomal fraction