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Opening the gate to the cell's recycling center

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 clam

Contact: Nancy Ross-Flanigan
University of Michigan

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