Considering its complex and extensive nature, it is surprising that the ER is one of the most dynamic organelles within the cell. ER tubules are constantly growing and retracting at an impressive rate, and the spider web-like rings within the ER will collapse and reform. This impressive array of dynamic ER movements would require a great deal of energy, which raises the question of their purpose and importance on the cellular level. Therefore, understanding the molecular machinery that governs these dynamics in greater detail has become a major goal in the lab.
Cos-7 cell expressing GFP-Sec61ß. A 2min movie with 5sec intervals was taken and sped up ~5 times. Notice extensive ER dynamics, including ER tubule growth, retraction, and ring rearrangements.
ER dynamics are known to occur along microtubules (MTs), and there are two distinct mechanisms that facilitate this movement. The more well characterized mechanism is termed Tip Attachment Complex (TAC), and this involves attaching the tip of an ER tubule to the growing (+) end of a microtubule. This occurs through the interaction of an ER integral membrane protein (STIM1) with a (+) end MT binding protein (EB1). Therefore as the MT grows, so does the ER tubule along with it. The other mechanism facilitating MT based ER dynamics is called ER-Sliding, and this is driven by the microtubule motor proteins kinesin-1 and dynein, but the mechanism of sliding dynamics remains an outstanding question. We have shown that sliding dynamics primarily occur on a subset of microtubules that are post-translationally acetylated. However we still do not understand how the ER attaches to these motor proteins, presumably there is an unknown adaptor that is an ER membrane protein. Additionally, can the same adaptor be used for anterograde and retrograde movements? Or are there multiple proteins that enable this movement. These are some of the mechanistic questions we wish to explore regarding ER dynamics.
Cos-7 cell expressing GFP-Sec61ß and mCh-αTubulin. Notice an ER sliding event occurs where a nascent ER tubule (green) grows out and trafficks along an already existing microtubule (red).
(Left) Cartoon representative of ER sliding and TAC mechanisms (adpated from Westrate et al. 2015, Annu. Rev. Biochem). (Right) Merged image of single ER network at timepoint t=0sec (red), t=30sec (green), t=60sec (blue)