Search

Am J Physiol Cell Physiol 298: C46-C55, 2010. First published November 4, 2009; doi:10.1152/ajpcell.00387.2009.--Acheron (Achn) was originally identified as novel gene that is induced when insect muscles become committed to die at the end of metamorphosis. In separate studies, we have demonstrated that Achn acts upstream of MyoD and is required by mammalian myoblasts to either differentiate or undergo apoptosis following loss of growth factors. In the present study we examined the role of Achn in regulating integrin-extracellular matrix interactions that are required for myogenesis. Both control [C.sub.2][C.sub.12] myoblasts and those engineered to express ectopic Achn expressed the fibronectin receptor integrin [[alpha].sub.5][[beta].sub.1] in the presence of growth factors and the laminin receptor [[alpha].sub.7][[beta].sub.1] following growth factor withdrawal. Expression of the laminin receptor was blocked in cells expressing either Achn antisense or an Achn deletion mutant that blocks differentiation. Control cells and those expressing ectopic Achn undergo sequential and transient increases in both substrate adhesion and migration before cell fusion. Blockade of Achn expression reduced these effects on laminin but not on fibronectin. Taken together, these data suggest that Achn may influence differentiation in part via its control of cell adhesion dynamics. [C.sub.2][C.sub.12]; differentiation; satellite cell; integrin signaling; skeletal muscle

Skeletal muscle atrophy and death are protracted processes that accompany aging and pathological insults in mammals. The intersegmental muscles (ISMs) from the tobacco hawkmoth Manduca sexta are composed of giant fibers that undergo distinct hormonally-regulated programs of atrophy and death at the end of metamorphosis. Atrophy occurs during the 3 days preceding adult emergence and results in a 40% reduction of mass, whereas death takes place during the subsequent 30 h and results in the complete loss of the fibers. There are no significant changes in tetanic force or calcium sensitivity in skinned fiber preparations during atrophy. However, the size of caffeine-induced contractions fell by about 50%. With the onset of the death phase, dramatic reductions occur in ISM: tetanic force, twitch amplitude, resting potential, caffeine-induced contractions, calcium sensitivity, and Hill coefficients. Several lines of evidence suggest that ISM atrophy is caused by an increase in protein turnover without significant modification of fiber organization. In contrast, ISM death is accompanied by disorganization of the contractile apparatus and concomitant loss of contractile function. Manduca; apoptosis; calcium; degeneration; sarcopenia

While there has been extensive work describing the timing, location and probable signals responsible for regulating programmed cell death (PCD) in the nervous system, relatively little is known about the molecular mechanisms that mediate this process. Several investigators have demonstrated that PCD in general, and neuronal PCD in particular, can be inhibited by drugs that arrest RNA or protein synthesis. These data have been interpreted as suggesting that de novo gene expression is required for cells to commit suicide. The general picture emerging from a number of experimental systems is that a variety of proteins can mediate the coupling of extracellular signals to a resident cell-death program. In this model, some of the components required for death are more or less constitutively present in the cell and await lineage-specific signals for their activation. A recent flood of papers has presented convincing evidence that the resident program for apoptosis in numerous cell types works via a series of essential proteases belonging to the CED-3/ICE family.

Nur77, a zinc finger transcription factor, is an essential mediator for apoptosis and is also involved in cell death. Nur77 can be expressed in response to T-cell antigen receptor's involvement in immature T cells and T-cell hybrids. Polyadenylation is observed on nur77 transcripts of condemned cells involved in cell death.

A study of intersegmental muscles (ISMs) of the tobacco hawkmoth Manduca sexta, which experience two sequential alterations in mass during metamorphosis indicates that two of the suppressed genes which are needed for the commitment of the muscles to die encode the proteins actin and myosin heavy chain. The repression of certain genes and the activation of others was assumed to be necessary for muscular commitment. After commitment, the expression of actin and myosin heavy chain mRNA significantly reduced. The quick dissolution of the muscles may be greatly influenced by the decrease in actin and myosin heavy chain synthesis.

The patterns of cell death displayed by T cells of the mouse thymus and the intersegmental muscles of the moth Manduca sexta were compared. It was found that they differ in terms of surface morphology, nuclear ultrastructure, DNA fragmentation and ubiquitin expression. The results suggestthat some cells may use a programmed cell death mechanism that is distinct fromapoptosis and that more than one cell death mechanism is used during development.