"In vivo" toxicity of a truncated version of the Drosophila Rst-IrreC protein is dependent on the presence of a glutamine-rich region in its intracellular domain

Abstract

The roughest-irregular chiasm C (rst-irreC) gene of Drosophila melanogaster encodes a transmembrane glycoprotein containing five immunoglobulin-like domains in its extracellular portion and an intracytoplasmic tail rich in serine and threonine as well some conserved motifs suggesting signal transduction activity. In the compound eye, loss-of-function rst-irreC mutants lack the characteristic wave of programmed cell death happening in early pupa and which is essential for the elimination of the surplus interommatidial cells. Here we report an investigation on the role played by the Rst-irreC molecule in triggering programmed cell death. ''In vivo'' transient expression assays showed that deletion of the last 80 amino acids of the carboxyl terminus produces a form of the protein that is highly toxic to larvae. This toxicity is suppressed if an additional 47 amino acid long, glutamine-rich region (''opa-like domain''), is also removed from the protein. The results suggest the possibility that the opa-like domain and the carboxyl terminus act in concert to modulate rstirreC function in apoptosis, and we discuss this implication in the context of the general mechanisms causing glutamine-rich neurodegenerative diseases in humans.

Precise temporal regulation of roughest is required for correct salivary gland autophagic cell death in Drosophila

“…It encodes a transmembrane glycoprotein with five Ig-like motifs in its extracellular domain sharing extensive similarity with several other immunoglobulin superfamily members from both Drosophila and vertebrates (Donoviel et al, 2001;Sellin et al, 2003;Strün-kelnberg et al, 2001Strün-kelnberg et al, , 2003Ueno et al, 2003). Although the Rst intracytoplasmic domain shows very little overall evolutionary conservation, it contains important structural motifs that have been implicated in signal transduction, such as a PDZ binding motif and a glutamine enriched sequence (Machado et al, 2002) as well as several potential serine, threonine, and tyrosine phoshorylation sites (Ramos et al, 1993). Mutants completely lacking the Rst protein develop more or less normally but display a very strong eye ''roughness'' due to the lack of apoptotic elimination of surplus interommatidial cells in the developing retina during early pupal stages, leading to the differentiation of excess secondary and tertiary pigment cells (Reiter et al, 1996;Wolf and Ready, 1991).…”

Processos celulares no desenvolvimento do olho composto de Apis mellifera

“…Em Drosophila, a proteína Roughest apresenta cinco domínios extracelulares do tipo imunoglobulina, os quais apresentam similaridade com domínios de diferentes proteínas de vertebrados. Na porção intracelular há uma região rica em glutaminas formando o domínio "opa-like" relacionado, em humanos, com importantes doenças neurodegenerativas como Huntington e Kennedy (Machado et al, 2002).…”

“…Em Drosophila, a proteína Roughest apresenta cinco domínios extracelulares do tipo imunoglobulina, os quais apresentam similaridade com domínios de diferentes proteínas de vertebrados. Na porção intracelular há uma região rica em glutaminas formando o domínio "opa-like" relacionado, em humanos, com importantes doenças neurodegenerativas como Huntington e Kennedy (Machado et al, 2002).A expressão desta proteína é essencial para o alinhamento das células interomatidiais que antecede a onda de apoptose no início da vida pupal. A perda desta função rst-irreC acarreta em quase total falha do programa de morte celular em remover células supérfluas que desorganizam a retina, as quais se diferenciam em células pigmentares dando ao olho uma aparência de "rugoso" (Wolff e Ready, 1991).…”