MOLECULAR MECHANISMS OF THE ELP COMPLEX AND ASSOCIATED FACTORS

University Of Washington, Seattle WA

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Abstract

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 lab has had a long-standing interest in understanding the molecular events underlying the activation of Rab proteins in membrane traffic, and we recently isolated the yeast homolog of IKAP, Elp1p, via a genetic screen to identify factors regulating Rab GTPase action. The FD syndrome protein is found in a complex with five other proteins, termed the Elongator complex. Our studies revealed an essential cytoplasmic role for the Elp complex in the regulation of polarized exocytosis [1]. Mutations in the human ELP1 gene are a cause of the neurological disorder Familial Dysautonomia. The long-term goal of the research is to elucidate the mechanism of the FD disease syndrome protein and the pathway leading from IKAP dysregulation to the clinical symptoms. The project proposed here is directed at understanding the molecular mechanisms by which Elp1p and the Elongator complex regulate polarized secretion and growth. To identify other genes and proteins that act in the Elp pathway we have conducted additional genetic screens that have resulted in the identification of a protein that is a potential target for altering growth control proteins via post-translational modification. Identification of the targets and modified entities in conjunction with the acetylation activities of Elp3p will help us understand the molecular mechanisms that regulate polarized secretion and cell growth.