Friday, 8 December 2017

Understanding Positioning System Of Cells May Help Unravel Key Diseases

An understanding of how molecules like RDGB control lipid composition may help to get an insight into complications that lead to cancers and neurodegenerative diseases.

By Ratneshwar Thakur Published in India Science Wire
Also appeared in The Hindu Globoble NetIndian Scroll BioVoice Firstpost Dainik Jagran

(L-R: Shweta, Rajan, Harini and Dr. Raghu)

In our day to day life, the global positioning system (GPS) helps us quickly determine our location and guides us to the preferred destination. Similarly, in living cells, molecules like proteins have their own positioning system which guides cells to coordinate their functioning and ensures the response. There is constant cross-talk among molecules in different compartments of the cell through such a positioning system.

Indian researchers are studying this positioning system in proteins like RDGB which ferry and move lipid molecules to maintain homeostatic levels of lipids in the plasma membrane. An understanding of how molecules like RDGB control lipid composition may help to get an insight into complications that lead to cancers and neurodegenerative diseases.

A team of researchers led by Dr. Padinjat Raghu at National Centre for Biological Sciences, Bangalore - have shown that signals present within RDGB protein determine if it will remain in a specific compartment of the cell for it to function normally. “This is important since, in the absence of such localization, the cellular function of this protein will be compromised,” researchers say in their study published in Journal of Cell Science.

“RDGB is known to localize at a specific location in the cell to maintain lipid composition of two closely situated membranes by transferring lipids from one compartment to the other. We want to understand how this process might be regulated,” pointed out Rajan Thakur, co-author of this study. The work has been done in fruit fly which has a simpler genome makeup and shares much of organizational principles of human cells.

Cells have thousands of molecules like proteins, lipids and carbohydrates and others, and still, every function is perfectly executed with respect to time, distance and their location. The new study explains that though different cellular structures perform specialized functions in seclusion, they do exchange information with each other to shape signaling output of the cell.

“In the absence of correct localization of RDGB protein to a very unique part of the cell, the photoreceptor cell does not function normally and fails to respond to light. We have found some key parts of the cellular positioning system that help in correct localization of RDGB protein,” said Dr. Raghu.

According to the study, cells have evolved ways to meet the requirement of organisms. For instance, specialized cells like photoreceptors have to process information over a large range of stimuli, from dim to very bright light. “These cells transduce the visual information at a fast pace by sequestering proteins near the light-sensitive membrane through robust positioning system,” said Shweta Yadav, first author in this study.

Dr. Raghu said, “We have discovered in fruit fly one key component of the positioning system that localizes RDGB is the protein, VAP. Mutations in human VAP have been identified in cases of a neurodegenerative disease called Amyotrophic Lateral Sclerosis (ALS).” He said this study might provide new insights into why patients with ALS undergo neurodegeneration leading to possible treatments.

The research team included Shweta Yadav, Rajan Thakur Harini K and Padinjat Raghu (NCBS, Bangalore); P. Georgiev (Babraham Institute, United Kingdom); S. Deivasigamani and G. Ratnaparkhi (IISER, Pune).

Friday, 1 December 2017

Scientists Discover How The Germline Stays Fresh

Germline abstains from transmitting damage starting with one age then onto the next - through damage-clearance mechanisms.

(Model Organism: C. elegans)
Living organisms age and die with time, and yet an animal species can continue indefinitely on account of its everlasting germ-cell lineage. Germ cell gives rise to the gametes of an organism that reproduces sexually and often said to be immortal because they are the link between generations. There has been a long historical interest in the immortality of the germ lineage. How is it that the somatic lineage perishes with an individual, but the germ lineage can survive across generations? This is a fundamental question in biology, which is not well understood. 

K. Adam Bohnert & Cynthia Kenyon, researchers from University of California and Calico Life Sciences, has discovered a possible explanation, using worms in their lab, regarding how human germlines are rejuvenated. The results of the study were published in the journal Nature. 

“An interesting, previous study by Jerome Goudeau and Hugo Aguilaniu demonstrated that protein carbonylation (a form of oxidative damage) is removed from C. elegans oocytes in a sperm-dependent manner, so we were curious whether we could watch such a clean-up process in live animals and understand molecularly how it would be controlled,” said K. Adam Bohnert.

According to the studies performed in C. elegans, there are damage-clearance mechanisms in the germline which prevent parental damage from being transmitted to progeny.

“In the study, we show that a coordinated shift in many aspects of oocyte physiology allows for a reversal in signs of aging, including protein aggregation. This occurs in a "just-in-time-fashion", as oocytes prepare for fertilization. This damage-removal process appears to clean the slate for each new generation, and may provide insight into one mechanism that helps the germ lineage stay immortal,” said Bohnert.

The finding is significant because humans have the similar lysosomal switch. However it is not known if the same progression followed in humans, but these initial finding has suggested that it is likely the case. If this is true in the case of human and other animals, this finding would solve the mystery- how the germline stays fresh.

“It is exciting to speculate that the natural rejuvenation strategies utilized by the germline could be co-opted to reverse signs of aging in other types of cells. It is possible that stem cells may be able to utilize similar clean-up machinery to eliminate molecular damage. We are also interested in whether a similar clean-up process occurs in the oocytes of other animals, including humans. If so, it is possible that this process may have relevance to human fertility,” said the Investigators.