Project Title

Cyclase-associated actin regulator capulet influences structural muscle proteins clearance in the Drosophila model of muscle atrophy

Presenters

Aaron AghaiFollow

Academic department under which the project should be listed

CSM - Molecular and Cellular Biology

Faculty Sponsor Name

Anton Bryantsev

Abstract (300 words maximum)

Muscle atrophy (MA) is a condition of muscle mass loss due to accelerated protein degradation in muscle fibers. Some pathological conditions, such as chronic inflammation or cancer, induce accelerated MA, which complicates medical treatment, hampers recovery of fragile patients, and ultimately can be the cause of a patient’s death. To gain better control over MA, more information is required about the whole spectrum of genetic factors that can influence MA.

Drosophila provides an excellent platform for genetic screening, although it has somewhat limited utility for MA research due to a lack of plasticity in insect muscles. We used Drosophila flight muscles to employ a model of simulated MA, in which experimentally induced muscle actin knockdown causes concomitant degradation of actin-associated proteins, such as tropomyosin (Tm) and troponin C (TpnC4). In parallel, actin-depleted muscles demonstrate upregulated expression of approximately 120 genes that could be potentially implicated in the accelerated removal of actin-associated proteins. Using these genes as candidates, we screened for those genes that had not been previously implicated in protein degradation but would have an effect on Tm and TnC4 clearance in actin-depleted muscles. One screen hit was produced by the gene capulet (capt), knockdown of which increased retained amounts of Tm and TpnC4 by 6-9 folds (40% vs 6% for Tm and 20% vs 2.5% for TnC4).

Capt codes for adenylate cyclase-associated protein, involved in actin filament dynamic regulation. We hypothesize that capt acts to promote actin depolymerization and contractile apparatus disassembly in the course of MA. Interestingly, elevated expression of the mammalian capt homolog (CAP1) has been reported for MA-inducing conditions: dermatomyositis in humans and muscle denervation in rats. Overall, our data indicate that capt could be a new conservative pro-MA factor.

Project Type

Oral Presentation (15-min time slots)

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Cyclase-associated actin regulator capulet influences structural muscle proteins clearance in the Drosophila model of muscle atrophy

Muscle atrophy (MA) is a condition of muscle mass loss due to accelerated protein degradation in muscle fibers. Some pathological conditions, such as chronic inflammation or cancer, induce accelerated MA, which complicates medical treatment, hampers recovery of fragile patients, and ultimately can be the cause of a patient’s death. To gain better control over MA, more information is required about the whole spectrum of genetic factors that can influence MA.

Drosophila provides an excellent platform for genetic screening, although it has somewhat limited utility for MA research due to a lack of plasticity in insect muscles. We used Drosophila flight muscles to employ a model of simulated MA, in which experimentally induced muscle actin knockdown causes concomitant degradation of actin-associated proteins, such as tropomyosin (Tm) and troponin C (TpnC4). In parallel, actin-depleted muscles demonstrate upregulated expression of approximately 120 genes that could be potentially implicated in the accelerated removal of actin-associated proteins. Using these genes as candidates, we screened for those genes that had not been previously implicated in protein degradation but would have an effect on Tm and TnC4 clearance in actin-depleted muscles. One screen hit was produced by the gene capulet (capt), knockdown of which increased retained amounts of Tm and TpnC4 by 6-9 folds (40% vs 6% for Tm and 20% vs 2.5% for TnC4).

Capt codes for adenylate cyclase-associated protein, involved in actin filament dynamic regulation. We hypothesize that capt acts to promote actin depolymerization and contractile apparatus disassembly in the course of MA. Interestingly, elevated expression of the mammalian capt homolog (CAP1) has been reported for MA-inducing conditions: dermatomyositis in humans and muscle denervation in rats. Overall, our data indicate that capt could be a new conservative pro-MA factor.