RESUMEN
One of the most challenging problems in developmental neurosciences is to understand the establishment and maintenance of specific membrane contacts between axonal, dendritic, and glial processes in the neuropils, which eventually secure neuronal connectivity. However, underlying cell recognition events are pivotal in other tissues as well. This brief review focuses on the pleiotropic functions of a small, evolutionarily conserved group of proteins of the immunoglobulin superfamily involved in cell recognition. In Drosophila, this protein family comprises Irregular chiasm C/Roughest (IrreC/Rst), Kin of irre (Kirre), and their interacting protein partners, Sticks and stones (SNS) and Hibris (Hbs). For simplicity, we propose to name this ensemble of proteins the irre cell recognition module (IRM) after the first identified member of this family. Here, we summarize evidence that the IRM proteins function together in various cellular interactions, including myoblast fusion, cell sorting, axonal pathfinding, and target recognition in the optic neuropils of Drosophila. Understanding IRM protein function will help to unravel the epigenetic rules by which the intricate neurite networks in sensory neuropils are formed.
Asunto(s)
Proteínas de Drosophila/fisiología , Drosophila/citología , Secuencia de Aminoácidos , Animales , Moléculas de Adhesión Celular Neuronal , Fusión Celular , Drosophila/embriología , Ojo/embriología , Proteínas del Ojo , Mioblastos Esqueléticos/citología , Neuronas/citología , Estructura Terciaria de Proteína , Especificidad de la EspecieRESUMEN
The rolling pebbles gene of Drosophila encodes two proteins, one of which, Rols7, is essential for myoblast fusion. In addition, Rols 7 is expressed during myofibrillogenesis and in the mature muscles. Here it overlaps with alpha-Actinin (alpha-Actn) and the N-terminus of D-Titin/Kettin/Zormin in the Z-line of the sarcomeres. In the attachment sites of the somatic muscles, Rols7 and the immunoglobulin superfamily protein Dumbfounded/Kin of irreC (Duf/Kirre) colocalise. As Duf/Kirre is detectable only transiently, it may be involved in establishing the first contact of the outgrowing muscle fiber to the epidermal attachment site. We propose that Rols7 and Duf/Kirre link the terminal Z-disc to the cell membrane by direct interaction. This is supported by the fact that in yeast two hybrid assays the tetratricopeptide repeat E (TPR E) of Rols7 shows interaction with the intracellular domain of Duf/Kirre. The colocalisation of Rols7 with alpha-Actn and with D-Titin/Kettin/Zormin in the Z-dics is reflected in interactions with different domains of Rols7 in this assay. In summary, these data show that besides the role in myoblast fusion, Rols7 is a scaffold protein during myofibrillogenesis and in the Z-line of the sarcomere as well as in the terminal Z-disc linking the muscle to the epidermal attachment sites.
Asunto(s)
Actinina/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Musculares/metabolismo , Músculo Esquelético/metabolismo , Sarcómeros/metabolismo , Animales , Diferenciación Celular/fisiología , Conectina , Proteínas del Citoesqueleto/metabolismo , Drosophila , Regulación de la Expresión Génica/fisiología , Sustancias Macromoleculares/metabolismo , Contracción Muscular/fisiología , Músculo Esquelético/embriología , Músculo Esquelético/ultraestructura , Mioblastos Esqueléticos/metabolismo , Mioblastos Esqueléticos/ultraestructura , Unión Proteica/fisiología , Estructura Terciaria de Proteína/fisiología , Sarcómeros/ultraestructura , Técnicas del Sistema de Dos HíbridosRESUMEN
The Drosophila cell adhesion molecule Rst plays key roles during the development of the embryonic musculature, spacing of ommatidia in the compound eye and of sensory organs on the antenna, as well as in the neuronal wiring of the optic lobe. In rst(CT) mutants lacking the cytoplasmic domain of the Rst protein, cell sorting and apoptosis in the eye are affected, suggesting a requirement of this domain for Rst function. To identify potential interacting proteins, yeast two-hybrid screens were performed using the cytoplasmic domains of Rst and its paralogue Kirre as baits. Among several putative interactors, two paralogous Drosophila PDZ motif proteins related to X11/Mint were identified. X11/Mint family members in C. elegans (LIN-10) and vertebrates are believed to function as adaptor proteins and to regulate the assembly of multi-subunit complexes at the synapse, thereby linking the vesicle cycle to cell adhesion. Using genetic, cell biological, and biochemical approaches, we show that the interaction of Rst with X11Lalpha is of biological significance. The proteins interact, for example, in the context of cell sorting in the pupal retina.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Moléculas de Adhesión Celular Neuronal/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila/metabolismo , Proteínas del Ojo/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Adhesión Celular , Moléculas de Adhesión Celular , Moléculas de Adhesión Celular Neuronal/genética , Drosophila/embriología , Proteínas de Drosophila/genética , Evolución Molecular , Ojo/embriología , Ojo/metabolismo , Proteínas del Ojo/genética , Microscopía Confocal , Modelos Genéticos , Proteínas Nucleares/genética , Filogenia , Isoformas de Proteínas/metabolismo , Estructura Terciaria de Proteína/genética , Pupa/crecimiento & desarrollo , Técnicas del Sistema de Dos HíbridosRESUMEN
The D. melanogaster rst and kirre genes encode two highly related immunoglobulin-like cell adhesion molecules that function redundantly during embryonic muscle development. The two genes appear to be derived from a common ancestor by gene duplication. Gene duplications have been proposed to be of major evolutionary significance since duplicated redundant sequences can accumulate mutations without detrimental effects for the organism and leave the duplicated genes free to assume novel functions. To address the issue of conservation of the duplicated sequences and their putative redundancy, as well as to identify putative functional divergence of the paralogs during drosophilid evolution, we performed an interspecies comparison of the rst and kirre genes from D. virilis and D. melanogaster. The D. virilis genome contains orthologues of both rst and kirre and hence the duplication took place before the split of the two lineages and has subsequently been conserved. However, whilst the Rst orthologues show a high degree of sequence similarity, this similarity is lower in Kirre orthologues. Especially the intracellular domains of D. virilis and D. melanogaster Kirre sequences are highly divergent: the D. virilis kirre gene lacks the 3'-most exon present in D. melanogaster, which contains motifs conserved between kirre and rst in D. melanogaster. Hence, while each of the two genes is highly conserved at the level of its exon-intron organization, the selection forces acting on the rst and kirre coding sequences are different. These findings are discussed in the light of general evolutionary mechanisms.