Endoplasmic Reticulum Structure and Function

Our recent focus has been on the organization, structure, and function of the Endoplasmic Reticulum.  The ER is a highly dynamic organelle that exists as an interconnected network of tubes and sheets. While ER sheets are mostly perinuclear and contiguous with the outer nuclear membrane, peripheral tubular extensions of the ER move along microtubule tracks, and frequently join together by membrane fusion. Regions of the peripheral ER maintain close contact with virtually all other cytoplasmic organelles. Membrane fusion allows the ER to maintain a dynamic network that can quickly change shape and preserve lumen continuity while adapting to the changing cytoplasmic environment. Insight into how ER fusion occurs was recently revealed by the identification of a membrane fusion protein called atlastin. In vitro and in vivo evidence suggest that atlastin is responsible for generating and maintaining the dynamic nature of peripheral ER tubules . In addition, atlastin dysfunction results in a form of Hereditary Spastic Paraplegia (HSP), a group of inherited neurological disorders characterized by progressive lower extremity weakness and spasticity. Several gene products that result in HSP including atlastin, affect ER morphology suggesting that ongoing shape changes and lumen continuity are important for normal ER function, and that loss of these could be implicated in a disease state.

We are currently examining the mechanism of atlastin mediated membrane fusion both in vitro and in vivo. Additionally, we are examining the role of atlastin and the ER tubule forming protein reticulon in synaptic function in Drosophila melanogaster.