New insights into communication systems within cells in a Fruit fly model
28 Aug 2015
Credit: NCBS Press release
Greasing the wheels of information transfer in cells
By Anusha Krishnan
Have you ever observed a café, a darshini or a dhaba during mealtimes? The seemingly chaotic scenes of shouted orders and responses are actually amazing communication systems that co-ordinate the serving of food from kitchens, removing used cutlery and resetting tables. The interior of a cell is much like a busy eatery in that it also needs seamless information exchange between its various parts – the information storage hub at the nucleus, the plasma membrane that co-ordinates signalling, and the protein and fat manufactories that maintain the plasma membrane.
One of the mysteries of within-cell communication is how the plasma membrane ‘resets’ itself after a bout of signalling – a process that alters its chemical structure. The answers to this question are emerging in part through a new study by a group of scientists from the National Centre for Biological Sciences (NCBS, Bangalore), Babraham Institute (Cambridge, UK) and University College London (UK). Their work has uncovered a key player in the communication network within a cell – a protein named “RDGBα”. The researchers used the light-sensitive cells of fruit fly eyes as a model system to investigate how this protein helps in maintaining the signalling networks of the plasma membrane.
The first step in converting light signals into electrical signals in photoreceptor cells (the cells in eyes that detect light) requires a stream of chemical reactions. This process alters the chemical properties of the plasma membrane due to a sequence of events referred to as the Phosphatidyl Inositol or PI cycle. The PI cycle also functions in many other instances, one of which is when cells in our body respond to rising blood sugar after a meal. During the PI cycle, a molecule within the cell membrane, named phosphatidylinositol bisphosphate (PtdInsP2) is broken down to release a by-product called phosphatidic acid (PtOH).
For the signalling cycle to continue, constant replenishment of PtdInsP2 and steady removal of PtOH from the membrane is a must. The generation of PtdInsP2 depends on another molecule, Phosphatidyl inositol (PtdIns), which is produced in another distinct compartment of the cell called the endoplasmic reticulum. The matter is further complicated by the fact that PtdIns and PtOH are lipids (which belong to the family of fats), and so, they cannot move by simple diffusion through the watery interior of the cell.
The answer to this problem lies in the protein RDGB α, which acts as a shuttle in delivering PtdIns to the plasma membrane and removing the PtOH byproduct to maintain a continuously functioning signalling system. Fruit flies with defective RDGBα function have photoreceptors that are defective in responding to light. These flies’ retinas also degenerate on continued exposure to light. Investigations revealed that the role of RDGBα in maintaining the chemical integrity and function of the plasma membrane is critical for normal photoreceptor structure and function.
“There has been considerable interest in the sequencing of the human genome and unravelling how encoded genes function in in health and disease. For obvious reasons there are limitations to detailed experimental analysis in humans. A recent study on the human equivalent of RDGB in cultured cells has showed that the protein functions in a similar manner to Drosophila RDGB. Therefore, our work demonstrating the importance of this protein in intact functioning flies highlights the value of genetic models such as Drosophila in dissecting human gene function.” says Dr. Padinjat, one of the corresponding authors in this work.
The process under study is a widely conserved chemical reaction which functions within many of the cellular communication pathways. Several of these are implicated in the development of diseases such as diabetes, tumour growth and even neurodegeneration. This study helps us understand how fundamental biochemistry operates in mediating information transfer within animal cells. In the future, comprehending these elementary processes may help in developing therapeutic strategies for human or animal diseases.
About the Authors:
Shweta Yadav , Aniruddha Panda and Swarna Mathre are affiliated to the National Centre for Biological Sciences (NCBS), Bangalore.
Kathryn Garner, Michelle Li, Evelyn Gomez-Espinosa and Shamshad Cockcroft are affiliated to the Department of Neuroscience, Physiology and Pharmacology, University College, London, UK
Plamen Georgiev and Hanneke Okkenhaug are affiliated to the Inositide Laboratory, Babraham Institute, Cambridge, UK.
Dr. Raghu Padinjat is affiliated to National Centre for Biological Sciences (NCBS), Bangalore.
Padinjat Raghu: firstname.lastname@example.org
The paper was published in the Journal of Cell Science on the 1st of September and can be read here.
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