Structural Study of Arc and Its Interactions with Endocytic Binding Partners

Abstract

Alzheimer's disease is a devastating neurodegenerative disease that causes great hardship to afflicted individuals as well as their caregivers. Currently available treatments seek to slow the disease's progression, but there is no known cure. Recent studies have shown that the activity‐regulated cytoskeleton‐associated protein Arc could act as a potential new drug target for the treatment of Alzheimer's disease. The Arc gene is an immediate early gene whose expression is induced by neuronal activation. Its expression is essential for memory consolidation. Behavioral studies of Arc−/− mice in implicit and explicit learning tasks demonstrate deficits in long‐term memory formation, though short‐term memory is unaffected. Still, the mechanism of Arc's role in memory formation is unknown. Previous studies have identified the endocytic proteins dynamin and endophilin as binding partners of the Arc protein. Dynamin is a large GTPase that plays a role in pinching off and fissioning the membrane during endocytosis as well as recruitment other proteins involved in endosome formation. Endophilin is implicated in vesicle formation and function in the brain. Arc interacts with both dynamin and endophilin to enhance AMPA receptor endocytosis and decrease surface expression. In this study, we have produced fragment proteins of dynamin, endophilin, and Arc using the E. coli expression system, and we have collected structural data on these proteins and aim to identify their structures and interactions.Support or Funding InformationThis project is sponsored by the grants from the National Institute of Health (NIGMS‐INBRE III, award number: P20GM103466; NIGMS‐AREA, award number: 1R15GM126499‐01) and the Hawaii Community Foundation (Alan M. Krassner Fund, award number: 16ADVC‐78888). The content is solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health or the Hawaii Community Foundation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.