Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Getting turned on

18.03.2010
Scientists discover switch mechanism for controlling traffic in cells

Scientists have identified a mechanism that switches on an extremely important process for the proper functioning and survival of our body's cells.

Specifically, the fast-track transportation pathway of 'cargo' to and from the surface of the cell. Defects in this trafficking pathway can have severe consequences, leading to numerous diseases such as high cholesterol, neuropathies, sterility and complications in immune response. Understanding the mechanisms underlying these disorders is crucial to developing possible treatments and new therapeutic strategies.

Dr. Peter McPherson and Dr. Brigitte Ritter and their colleagues have discovered how a molecule called Rab35, which acts as a switch is turned on in order to activate the fast-track recycling pathway – in which cargo that needs to be recycled back to the surface of the cell is rapidly selected and transported. The new study, published in the prestigious journal Molecular Cell, was conducted at The Montreal Neurological Institute and Hospital – The Neuro, McGill University.

"The cells that make up our bodies are like a busy city," says Dr. McPherson, neuroscientist at The Neuro and the co-principal investigator for the study. "The cell surface is defined by a membrane that separates its interior from the external world, like the walls or borders of a city. Within this environment, there are simultaneous trafficking pathways that transport vital nutrients, receptors and other components required for cells to function, within cargo vehicles called 'vesicles.' Like traffic in a city, these 'cargo' vesicles travel at different speeds to numerous destinations within the cell with different purposes. For example, the receptors on the cell surface that bind to cholesterol are on the fast track pathway, so that once they deliver the cholesterol inside the cell, they move back to the surface quickly so that they can pick up some more. It is therefore crucial to understand the controls and switching mechanisms of trafficking inside cells, as this system is of vital importance to the proper functioning of the body."

The Rab35 molecule is the trafficking switch for the fast-track or high-priority recycling pathway signaling the quick return of cargo to the cell surface membrane. It is known that Rab35 exists in two forms, 'on' (GTP- bound) or off (GDP- bound). When Rab35 is turned 'on', it allows the cargo to go back up to the cell surface. What Dr. McPherson and Dr. Ritter and colleagues have discovered is the switch that turns Rab35 on.

"In this study we identified that a particular region of the vesicle-bound protein connecden, , called the DENN domain, is the 'finger' that flips the switch," says Dr. Ritter. "The DENN domain connects with the Rab35 molecule and through enzymatic activity converts Rab35 from the inactive to the active form, in essence, turning on the switch."

DENN domains are found in multiple protein products encoded by 16 human genes. Mutations in the DENN domain cause humans diseases such as sterility and Charcot-Marie-Tooth neuropathy, yet until now the function of this common module has been unknown. The DENN domain is evolutionarily ancient and bioinformatics studies suggest that it is present in all eukaryotic, or multi-compartmental cells, indicating that the DENN domain has mediated crucial functions throughout evolution.

"If the finger or the switch itself is mutated or missing, cargo can't recycle, which has dire consequences," adds Dr. McPherson. "For example a very important cargo transported by this specific fast track recycling pathway, controlled by Rab35 is the MHC class I receptor involved in the immune system response. If a cell becomes infected by a virus, the MHC receptor is loaded with fragments of the virus that have infected the inside of a cell. The MHC receptor needs to be taken back to the cell surface quickly so that so that it can act as a signpost indicating to circulating immune cells that this particular cell has been infected by a virus and needs to be destroyed, preventing viral infection to other cells."

This critical new insight into the control mechanisms for the cells' trafficking system provide a deeper understanding of diseases that result from complications in trafficking, as well as provide new therapeutic targets for the development of treatments.

This study was supported by the Fonds de la recherche en santé du Québec (FRSQ), the Canadian Institutes of Health Research (CIHR) and the National Institutes of Health (NIH).

About the Montreal Neurological Institute and Hospital:

The Montreal Neurological Institute and Hospital - The Neuro is a unique academic medical centre dedicated to neuroscience. The Neuro is a research and teaching institute of McGill University and forms the basis for the Neuroscience Mission of the McGill University Health Centre. Founded in 1934 by the renowned Dr. Wilder Penfield, The Neuro is recognized internationally for integrating research, compassionate patient care and advanced training, all key to advances in science and medicine. Neuro researchers are world leaders in cellular and molecular neuroscience, brain imaging, cognitive neuroscience and the study and treatment of epilepsy, multiple sclerosis and neuromuscular disorders. For more information, please visit www.mni.mcgill.ca.

Anita Kar | EurekAlert!
Further information:
http://www.mni.mcgill.ca
http://www.mcgill.ca

More articles from Studies and Analyses:

nachricht Antarctic Ice Sheet mass loss has increased
14.06.2018 | Technische Universität Dresden

nachricht WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Temperature-controlled fiber-optic light source with liquid core

In a recent publication in the renowned journal Optica, scientists of Leibniz-Institute of Photonic Technology (Leibniz IPHT) in Jena showed that they can accurately control the optical properties of liquid-core fiber lasers and therefore their spectral band width by temperature and pressure tuning.

Already last year, the researchers provided experimental proof of a new dynamic of hybrid solitons– temporally and spectrally stationary light waves resulting...

Im Focus: Overdosing on Calcium

Nano crystals impact stem cell fate during bone formation

Scientists from the University of Freiburg and the University of Basel identified a master regulator for bone regeneration. Prasad Shastri, Professor of...

Im Focus: AchemAsia 2019 will take place in Shanghai

Moving into its fourth decade, AchemAsia is setting out for new horizons: The International Expo and Innovation Forum for Sustainable Chemical Production will take place from 21-23 May 2019 in Shanghai, China. With an updated event profile, the eleventh edition focusses on topics that are especially relevant for the Chinese process industry, putting a strong emphasis on sustainability and innovation.

Founded in 1989 as a spin-off of ACHEMA to cater to the needs of China’s then developing industry, AchemAsia has since grown into a platform where the latest...

Im Focus: First real-time test of Li-Fi utilization for the industrial Internet of Things

The BMBF-funded OWICELLS project was successfully completed with a final presentation at the BMW plant in Munich. The presentation demonstrated a Li-Fi communication with a mobile robot, while the robot carried out usual production processes (welding, moving and testing parts) in a 5x5m² production cell. The robust, optical wireless transmission is based on spatial diversity; in other words, data is sent and received simultaneously by several LEDs and several photodiodes. The system can transmit data at more than 100 Mbit/s and five milliseconds latency.

Modern production technologies in the automobile industry must become more flexible in order to fulfil individual customer requirements.

Im Focus: Sharp images with flexible fibers

An international team of scientists has discovered a new way to transfer image information through multimodal fibers with almost no distortion - even if the fiber is bent. The results of the study, to which scientist from the Leibniz-Institute of Photonic Technology Jena (Leibniz IPHT) contributed, were published on 6thJune in the highly-cited journal Physical Review Letters.

Endoscopes allow doctors to see into a patient’s body like through a keyhole. Typically, the images are transmitted via a bundle of several hundreds of optical...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Munich conference on asteroid detection, tracking and defense

13.06.2018 | Event News

2nd International Baltic Earth Conference in Denmark: “The Baltic Sea region in Transition”

08.06.2018 | Event News

ISEKI_Food 2018: Conference with Holistic View of Food Production

05.06.2018 | Event News

 
Latest News

Graphene assembled film shows higher thermal conductivity than graphite film

22.06.2018 | Materials Sciences

Fast rising bedrock below West Antarctica reveals an extremely fluid Earth mantle

22.06.2018 | Earth Sciences

Zebrafish's near 360 degree UV-vision knocks stripes off Google Street View

22.06.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>