How Does an Organelle get its Shape?

The endoplasmic reticulum is a large membrane-bound organelle that is composed of distinct structural domains including cisternae, tubules, and the nuclear envelope. This elaborate structure allows the ER to extend throughout the entirety of the cytoplasm but despite its breadth and complexity; the ER maintains a single continuous lumen. We are studying how proteins generate and maintain the shape of the various ER domains as well as the functional significance of these domains. Our first mechanistic insight came with the discovery of the Reticulon and DP1/Yop1 family of proteins (Voeltz et al. 2006). These are specialized membrane bound proteins that generate and stabilize the tubular shape of the peripheral ER, as well as help to maintain the curvature at edges of ER cisternae. However, the mechanisms responsible for generating and maintaining ER cisternae are still poorly understood and an interesting question for the future.

Cos-7 cell expressing mCh-Sec61ß. Notice 3 domains of ER; Nuclear envelope, Tubules, and Cisternae

The ER is exceptional in that it contains several defined structural domains, yet it is constantly rearranging its structure. How is the ER able to rapidly alter its structure, and what purpose do these rearrangements serve? Additionally, are the various machineries (such as reticulons) regulated in order to facilitate the dynamic nature of the ER? The importance of these processes is evident during cell division, when the ER undergoes a massive structural rearrangement. The nuclear envelope collapses and the elaborate peripheral ER is reorganized in a manner that does not interfere with chromosome segregation or proper inheritance of organelles into the daughter cell. We hope to work towards understanding the mechanisms responsible for forming various structural domains within the ER and how their dynamic rearrangements are regulated.

Cos-7 cell expressing mCh-Sec61ß (red) and Rtn4a-GFP (green). Notice proliferation of ER tubules and ER tubule bundles due to Rtn4a overexpression.

View our other research projects: