This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our research group has recently connected two fundamental cellular processes that have not previously been linked ? the biogenesis and organization of mitochondrial and secretory pathway compartments. Of particular relevance to this proposal is the observation that the genes that connect the organization of mitochondria with the secretory pathway are the molecular bases for two related genetic neurological diseases in humans, Cohen syndrome and choreoacanthocytosis. Based solely on the previous work in yeast, inactivation of these genes in humans has been presumed to alter the secretory pathway in neural cells, resulting in the observed pathologies in affected individuals. We hypothesize that upon inactivation of one or more of these genes, both mitochondrial and secretory pathway compartments are structurally and spatially altered. This proposal describes experimental tests of this hypothesis in human cells through the use of molecular reagents that will reduce, over-express, and localize the gene product responsible for choreoacanthocytosis in humans.
Showing the most recent 10 out of 325 publications
