Calcium channel discovery solves molecular mystery
24 April 2009
An international team of scientists, including researchers from the University of Edinburgh and the University of Oxford, has discovered two protein channels that control the flow of calcium in cells. The channels are opened by a cell messenger called nicotinic acid adenine dinucleotide phosphate (NAADP).
Although it has been known to affect calcium release, the exact role and function of NAADP has been a mystery to scientists since it was discovered 15 years ago.
In the new study, the researchers show that NAADP controls the two protein channels, regulating a store of calcium held in lysosomes (capsules found in cells that contain digestive enzymes, which are also regulated by calcium).
“The discovery could help us to design drugs to combat diabetes and the other myriad diseases where calcium signals are disrupted,” said Professor Antony Galione, Head of Pharmacology at the University of Oxford. Studies have shown that inhibition of the channels in cells of the pancreas causes major disruption to the secretion of insulin.
The researchers also showed that lysosomes are able to carry the two channels to different parts of the cell, helping to regulate different cell processes.
“We’ve shown that the lysosome, which was thought to only be the dustbin of the cell, plays a vital role in directing cellular messages,” said Dr John Parrington, one of the researchers from the University of Oxford. “This is important because some diseases that affect the brain are due to the dustbin failing to be emptied properly.”
Dr Mark Evans, another of the researchers, from the University of Edinburgh’s Centre for Integrative Physiology, said: “These findings could allow us to unpick the complex pathways that regulate processes from fertilisation of eggs to cell growth, division and ultimately cell death.”
Image: Stereocilia on the outer hair cells of the cochlea. When the stereocilia are deflected by sound, the fine tip links that connect them are stretched, opening channels for potassium and calcium ions to flow into the cell. This sets off nerve signals that carry the sound information to the brain.
Credit: Dr David Furness, Wellcome Images
Reference
Calcraft PJ et al. NAADP mobilizes calcium from acidic organelles through two-pore channels. Nature 23 March 2009 [epub ahead of print].