Proceedings of The Physiological Society

University of Cambridge (2008) Proc Physiol Soc 11, PC139

Poster Communications

Disruption of an integrin-containing muscle adhesion complex causes muscle protein degradation in Caenorhabditis elegans

E. A. Oczypok2,1, L. A. Jacobson2, N. J. Szewczyk1,2

1. School of Graduate Entry Medicine & Health, University of Nottingham, Derby, England, United Kingdom. 2. Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

Continuous transmission of mechanical signals (mechanotransduction) is required for maintenance of muscle protein mass (1). Of the many factors that cause muscle wasting in human beings, spaceflight and immobilization are thought to induce wasting via decreased use, possibly via decreased mechanotransduction. However, the nature and scope of the mechanical linkage to intracellular signalling pathways regulating protein mass are largely unknown. Proteins making up worm focal adhesions (known as dense bodies) are present in decreased amounts following spaceflight (2-3); these changes correlate with a post-flight movement defect (2). We conducted a series of experiments on the ground in order to examine the significance of this correlation. We find that acute treatment of adult C. elegans with RNAi against one of these genes, unc-97 (PINCH/LIM-domain), causes degradation of a reporter protein in muscle cytosol. Acute RNAi treatment against any of another eight genes, whose products are likewise conserved members of an integrin-containing muscle adhesion complex, also causes degradation. Suggesting specificity in the regulation of degradation, we find that RNAi against the gene for another complex member, unc-95 (LIM-domain), fails to cause muscle protein degradation even though it causes a movement defect. Experiments using temperature-sensitive mutations in two of these genes, either unc-112 (MIG-2) or unc-52 (Perlican), confirm that disruption of this complex causes degradation, and further show that the extramuscular ligand (UNC-52/Perlican) is required to prevent degradation. In these mutants movement becomes uncoordinated and muscle structure is disrupted following temperature shift. In C. elegans, Acetylcholine Receptor and opposed Insulin Growth Factor Receptor-Fibroblast Growth Factor Receptor signalling networks control muscle protein degradation via proteasome and non-proteasome dependent mechanisms, respectively (4-5). Drugs, mutations, and RNAi treatments targeted at these networks, and known to block degradation in C. elegans muscle, fail to block degradation triggered by acute loss of members of the muscle attachment complex. Current goals include determining the identity and regulation of the relevant protease(s).

Where applicable, experiments conform with Society ethical requirements