By Brian Foley / UChicago News
Protein lets calcium ions into cell; finding could open new avenues for therapies
Lysosomes, often reductively referred to as the "garbage disposals" of cells, play a pivotal role in our cells’ digestive systems by getting rid of unwanted materials.
Now in a groundbreaking study, researchers from the laboratory of Prof. Yamuna Krishnan at the University of Chicago have identified the protein responsible for a key role in how lysosomes work: how calcium ions get into lysosomes.
Published in Science Advances on February 15th, their research represents a significant step forward in understanding the intricate mechanisms underlying lysosomal calcium regulation—and opens new avenues for therapies for diseases that involve lysosome function, including diseases like Parkinson’s or ALS.
Finding the transporter
The function of lysosomes is tightly regulated by complex cellular signals, including calcium ions moving into and out of lysosomes.
Scientists have known how lysosomes release their calcium since their discovery in the 1950s by Christian René de Duve. What has received less attention is how lysosomes refill their calcium back up.
“Part of the problem has been an inability to measure calcium inside the lysosome,” said Matthew Zajac, PhD’22, the first author of the paper. “Because it's a highly acidic compartment, it's been hard to measure the calcium without that acidity interfering with measurements.”
It wasn’t until the Krishnan lab developed their own pH-correctable sensing device called CalipHluor, a device that can report calcium concentrations in acidic organelles, that the group had a method to accomplish their goal.
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