Acheron, a novel member of the Lupus Antigen family, is induced during the programmed cell death of skeletal muscles in the moth Manduca sexta

Abstract

In order to identify novel genes associated with the initiation of programmed cell death during development, we employed a differential screening protocol to isolate cDNAs that were induced when the intersegmental muscles (ISM) of the moth Manduca sexta become committed to die at the end of metamorphosis. In this report we provide the first description of Acheron (Achn), a novel protein that was isolated in this screen. Acheron contains three Lupus antigen (La) repeats, nuclear localization and export (NLS and NES) signals, and an RNA recognition motif. Achn defines a new subfamily of La proteins that appears to have branched from authentic La protein relatively late in metazoan evolution. Achn is widely expressed in various insect, mouse and human tissues. Consistent with its expression during ISM death, Achn has been shown in separate studies to control muscle differentiation and apoptosis in both mice and zebrafish. These data define Achn as a newly discovered regulatory molecule that presumably mediates a variety of developmental and homeostatic processes in animals.

Acheron, an novel LA antigen family member, binds to cask and forms a complex with id transcription factors

“…Yeast two-hybrid screen Human Acheron cDNA (Achn) [1] lacking the coding region for the first 33 amino acids, was amplified by PCR with primers containing the SalI restriction sites and subcloned in frame to SalI site of pAS2-1 to form pAS2-1-Achn as the bait. pAS2-1-Achn Achn was transformed into yeast CG1945 and the expression of the fusion protein verified by Western blotting using an anti-Achn antiserum [1].…”

“…Acheron (Achn) is a newly described protein that is structurally related to the LA/SSB (Lupus antigen/Sjőgren Syndrome) protein but defines a distinct subfamily that is highly conserved across phylogeny [1]. This 64 kDa protein contains a highly conserved N-terminal three imperfect Lupus antigen (LA) repeats consisting of 71 amino acids (amino acids 99-171), RNA recognition motif (amino acids 184-296), an RNA binding motif, and functional nuclear localization and export signals.…”

“…As well, it has several putative phosphorylation and amidation sites. Achn was identified as a novel death-associated transcript from the intersegmental muscles (ISMs) of the moth Manduca sexta [1]. Moth and human Achn display 31% identity and 40% similarity overall, and 42% identity and 54% similarity in a conserved 227 amino acid region [1].…”

“…Achn was identified as a novel death-associated transcript from the intersegmental muscles (ISMs) of the moth Manduca sexta [1]. Moth and human Achn display 31% identity and 40% similarity overall, and 42% identity and 54% similarity in a conserved 227 amino acid region [1]. Western blot analysis of mouse tissue has shown that Achn is most widely expressed in neurons and skeletal muscle [1].…”

“…Moth and human Achn display 31% identity and 40% similarity overall, and 42% identity and 54% similarity in a conserved 227 amino acid region [1]. Western blot analysis of mouse tissue has shown that Achn is most widely expressed in neurons and skeletal muscle [1]. Developmental studies in zebrafish embryos and mouse myoblasts have demonstrated that Achn acts upstream of the muscle specific transcription factor MyoD and plays an essential role in myogenesis (Wang, Z., Glenn, H., Liu, J.X., Seth, A., Karlstrom, R.O.…”