Navigation Links
Opening the gate to the cell's recycling center
Date:7/14/2010

ANN ARBOR, Mich.---In cells, as in cities, disposing of garbage and recycling anything that can be reused is an essential service. In both city and cell, health problems can arise when the process breaks down.

New research by University of Michigan cell biologist Haoxing Xu and colleagues reveals key details about how the cell's garbage dump and recycling center, the lysosome, functions. These insights, which may lead to better understanding of conditions such as amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease) and Charcot-Marie-Tooth (CMT) disease, suggest new avenues of treatment for these and other diseases that cause nerves and muscles to malfunction.

The research, published this week in the online, multidisciplinary journal Nature Communications, focused on gateways called calcium channels in the lysosome membrane. Calcium channels, which also are found in the membranes surrounding muscle and nerve cells, are made of proteins that respond to signals in the form of electrical impulses. When the proper signal comes along, the proteins open the channel, allowing calcium to pass through. The calcium, in turn, triggers some vital process such as muscle contraction or the release of a hormone or neurotransmitter (a chemical messenger involved in nerve transmission).

Scientists know a lot about the workings of calcium channels in the surfaces of muscle and nerve cells, but understanding what goes in the lysosome---a tiny pouch hidden inside the cell---has been a challenge, said Xu. Consequently, the exact identity of the protein involved and how it becomes activated have remained a mystery.

To explore the channel and its workings, Xu's group modified a technique known as the patch clamp, in which a scaled-down pipette and electrodes are attached to a cell membrane to record the activity of one or more proteins making up the channel. With their modification, which they call the lysosome patch clamp, the researchers determined that a protein called TRPML1 serves as the calcium channel in lysosomes and that a lipid known as PI(3,5)P2 carries the signal that activates the protein.

This particular protein and lipid aren't obscure characters previously unknown to science. A mutation in the gene that produces TRPML1 is known to cause Type IV mucolipidosis (ML4), a genetic disorder that affects mainly Jews of Eastern European background and results in mental retardation, poor vision and diminished motor abilities. And mutations in the enzymes needed to make PI(3,5) P2 cause a variety of neurodegenerative diseases including ALS and CMT.

The protein TRPML1 also is of interest because of the unusual way it does its work.

"While other channel proteins are in the 'passenger' seats of the membrane traffic, TRPML1 is in the 'driver' seat," said Xu, an assistant professor of molecular, cellular and developmental biology. This suggests that manipulating TRPML1 channel activity using channel activators or inhibitors could affect membrane traffic.

"If you can activate the channel, it might be possible to overcome the membrane traffic defects caused by the disease-causing mutations. Luckily, small-molecule chemicals that can stimulate TRPML1 channel activity are already available, " Xu said.

He and collaborator Miriam Meisler, a human genetics professor at the U-M Medical School, have experiments underway to see if they can prevent or reverse the course of disease in a mouse model of ALS by increasing activity of the TRPML1 channel.

If the strategy is successful, Xu hopes to explore its use in treating other neurological diseases.

"If the system we're studying turns out to be compromised in more common diseases, the method of increasing channel activity could have important implications for their treatment," he said.


'/>"/>

Contact: Nancy Ross-Flanigan
rossflan@umich.edu
734-647-1853
University of Michigan
Source:Eurekalert

Related biology news :

1. Tobacco plant thwarts caterpillar onslaught by opening flowers in the morning
2. Opening a new window on daylight
3. Less than one month to opening of world’s largest global congress on osteoporosis
4. Does the existing standard of care supply energy sources to brain tumor cells?
5. Mahjong gene is key player when cancer, normal cells compete
6. Improving clinical use of stem cells to repair heart damage
7. Mexican salamander helps uncover mysteries of stem cells and evolution
8. Neural stem cells attack glioblastoma cells
9. Caltech biologists discover how T cells make a commitment
10. Reprogrammed human blood cells show promise for disease research
11. UVA radiation damages DNA in human melanocyte skin cells and can lead to melanoma
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/2/2017)... Summary This report provides all the information you ... activities since 2010. ... Read the full report: http://www.reportlinker.com/p03605615-summary/view-report.html ... an in-depth insight into the partnering activity of one of ... company reports are prepared upon purchase to ensure inclusion of ...
(Date:3/2/2017)... Australian stem cell and regenerative medicine company, ... an agreement with the Monash Lung Biology Network, a ... and Department of Pharmacology at Monash University, ... to support the use of Cymerus™ mesenchymal stem cells ... Asthma is a chronic, long term lung condition recognised ...
(Date:2/28/2017)... -- News solutions for biometrics, bag drop and New ... At ... 16 March, Materna will present its complete end-to-end passenger journey, ... a real benefit for passengers. To accelerate the whole passenger ... point solutions to take passengers through the complete integrated process ...
Breaking Biology News(10 mins):
(Date:3/22/2017)... MONICA, Calif. , March 22, 2017 /PRNewswire/ ... are proud to announce their extended partnership and ... will be headlined by the 21 st ... BIOMEDevice Boston, taking place May 3-4, 2017. ... Advanced Medical Technology Association (ADVAMED) President and CEO, ...
(Date:3/22/2017)... 2017 Oramed Pharmaceuticals Inc. (NASDAQ: ... ), a clinical-stage pharmaceutical company focused ... announced today that Dr. Miriam Kidron , ... titled, "Oral Insulin for Diabetes Treatment: Bypassing the ... and Peptide Therapeutics (OPT) Boston Conference in ...
(Date:3/22/2017)... ALBANY, New York , March 22, 2017 /PRNewswire/ ... market is largely fragmented, states a research report by ... Sanofi S.A., Pfizer Inc., Amgen Inc., and AbbVie Inc., ... market in 2015. The prominent players in this market ... to expand their product portfolio, which is likely to ...
(Date:3/22/2017)... , March 22, 2017 /PRNewswire/ - FACIT ... (the "Company" or "Propellon"), a start-up created by ... anti-cancer therapeutics. FACIT,s investment, combined with non-dilutive capital, ... program. The seed funding enables Propellon to accelerate ... the Company for financing and/or entering a strategic ...
Breaking Biology Technology: