\ Researchers \ Calcineurin's Orchestral Manoeuvres in Muscle
Adult muscle cells must continually adapt to the stresses of their use or disuse. When a muscle’s repetitive workload is increased, it hypertrophies, adapting by becoming larger and more efficient. Unstressed muscles atrophy, becoming smaller and less efficient.
But Dr. Robin Michel, research director of the Neuromuscular Research Lab, Laurentian University, Ontario, says we are only beginning to understand the molecular instructions that cause these adaptive changes. “I am interested in how the skeletal muscle genes are expressed for adult cell growth and efficiency” he says. “It happens hand-in-hand.”
Muscle cells are long, multi-nucleated fibres. A skeletal (voluntary) muscle fibre contracts in response to the pulses it receives from the motor neuron. The muscle nuclei express different genes to produce different proteins in response to changes in their electrical and chemical experience from the neuron. Via complex signaling pathways, the muscle cells are able to sense changes in their workload and adapt accordingly.
This ability to sense change is where Michel believes calcineurin comes in. Calcium levels in the muscle cell oscillate in response to the pulses from the nerve and the contraction of the muscle. And calcineurin is a calcium-sensitive enzyme. “What I think happens is that calcineurin is a sensor of change,” says Michel. “Calcineurin is found in all muscle types. If calcium oscillations are above and beyond what the cell is accustomed to, then that pathway is triggered.”
Using “overload” mouse models, Michel creates an increased load on a muscle in the calf of the mouse by removing two adjacent muscles that normally share the work. Under the added stress, the muscle fibres hypertrophy, and become more efficient, shifting toward a slow fibre-type.
When Michel chemically blocked the action of calcineurin, the overloaded muscles did not hypertrophy. “We saw that calcineurin was a key molecule in how calcium oscillations will eventually lead to the expression of genes for growth, and also for transcription of more energy-efficient proteins,” he explains. “But we have always said calcineurin does not act alone in affecting growth. It has to co-operate with other pathways in parallel, or upstream and we intend to decipher those pathways. “
Already, Michel is elucidating other interactions with calcineurin. “Calcineurin seems to be at the nexus,” he says. “But it is like a perfect symphony. Calcineurin may be like the first violinist, but all of the instruments in the orchestra are playing together in tune.”
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Calcineurin's Orchestral Manoeuvres in Muscle
Adult muscle cells must continually adapt to the stresses of their use or disuse. When a muscle’s repetitive workload is increased, it hypertrophies, adapting by becoming larger and more efficient. Unstressed muscles atrophy, becoming smaller and less efficient. But Dr. Robin Michel, research director of the Neuromuscular Research Lab, Laurentian University, Ontario, says we are only beginning to understand the molecular instructions that cause these adaptive changes. “I am interested in how the skeletal muscle genes are expressed for adult cell growth and efficiency” he says. “It happens hand-in-hand.”
Muscle cells are long, multi-nucleated fibres. A skeletal (voluntary) muscle fibre contracts in response to the pulses it receives from the motor neuron. The muscle nuclei express different genes to produce different proteins in response to changes in their electrical and chemical experience from the neuron. Via complex signaling pathways, the muscle cells are able to sense changes in their workload and adapt accordingly.
This ability to sense change is where Michel believes calcineurin comes in. Calcium levels in the muscle cell oscillate in response to the pulses from the nerve and the contraction of the muscle. And calcineurin is a calcium-sensitive enzyme. “What I think happens is that calcineurin is a sensor of change,” says Michel. “Calcineurin is found in all muscle types. If calcium oscillations are above and beyond what the cell is accustomed to, then that pathway is triggered.”
Using “overload” mouse models, Michel creates an increased load on a muscle in the calf of the mouse by removing two adjacent muscles that normally share the work. Under the added stress, the muscle fibres hypertrophy, and become more efficient, shifting toward a slow fibre-type.
When Michel chemically blocked the action of calcineurin, the overloaded muscles did not hypertrophy. “We saw that calcineurin was a key molecule in how calcium oscillations will eventually lead to the expression of genes for growth, and also for transcription of more energy-efficient proteins,” he explains. “But we have always said calcineurin does not act alone in affecting growth. It has to co-operate with other pathways in parallel, or upstream and we intend to decipher those pathways. “
Already, Michel is elucidating other interactions with calcineurin. “Calcineurin seems to be at the nexus,” he says. “But it is like a perfect symphony. Calcineurin may be like the first violinist, but all of the instruments in the orchestra are playing together in tune.”
| Posted On: Monday, April 19, 2004 Modified: Thursday, April 22, 2004 Category: Researchers Posted By: |
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