The future is looking bright for optogenetics – a technique which uses light to control cellular processes. Following on from a previous illuminating study covered here at Epigenie (Shedding Light on Stem Cell Therapy for Parkinson’s with Optogenetics), another group of researchers have utilized optogenetics in a novel manner – the light-mediated control of sub-cellular localization of specific organelles.
Many important cellular events need the proper organization of these organelles along the cytoskeletal system, the framework of any given cells. Now researchers under the tutelage of Casper C. Hoogenraad and Lukas C. Kapitein (Utrecht University, The Netherlands) have uncovered a particularly “bright” method of controlling this organization in order to study and control cell function in a non-invasive manner.
How did they manage this feat? Through utilizing motor proteins which bind to the cytoskeleton, a special light sensitive protein, and protein localization signals for specific organelles. Let’s shine the spotlight on their work:
- Initial studies used PEX-LOV – a fusion between a peroxisomal targeting signal (PEX) and a photosensitive protein domain of phototropin 1 (LOV) found in Avena sativa (common oats!).
- Researchers co-expressed PEX-LOV alongside several different motor proteins fused to another engineered protein (ePDZb1) which can bind to LOV only after exposure to blue light.
- Using a Kinesin motor protein peroxisomes were relocated to the cell periphery.
- Using a Dynein motor protein peroxisomes were relocated to the cell center.
- Using Myosin-Vb motile peroxisomes were anchored in place.
- These processes required the presence of blue light, which was and was rapid and locally restricted allowing for tight spatiotemporal control of organelle movement.
Van Bergeijk et al then moved into primary cultures of rat hippocampal neurons and studied the effect of moving RAB11-positive endosomes, previously implicated in the control of neural cell axon growth. Light-induced coupling of Dynein to RAB11 shuttled endosomes towards the cell center and led to a reversible decrease in axon growth, while coupling Kinesin to RAB11 resulted in endosome movement to the cell periphery and rapid axon extension. This exciting experiment demonstrates that not only do endosomes have a key role in axon extension, but that this method of optogenic control is highly successful and could be used to modify neuronal cell function.
This technique should open the door for further studies on the important of organelle organization and perhaps even shed light how we can harness this potentially powerful technique to repair/regenerate damaged neural cells.