RESUMEN
We identify here a novel class of loss-of-function alleles of uncoordinated locomotion(unc)-108, which encodes the Caenorhabditis elegans homologue of the mammalian small guanosine triphosphatase Rab2. Like the previously isolated dominant-negative mutants, unc-108 loss-of-function mutant animals are defective in locomotion. In addition, they display unique defects in the removal of apoptotic cells, revealing a previously uncharacterized function for Rab2. unc-108 acts in neurons and engulfing cells to control locomotion and cell corpse removal, respectively, indicating that unc-108 has distinct functions in different cell types. Using time-lapse microscopy, we find that unc-108 promotes the degradation of engulfed cell corpses. It is required for the efficient recruitment and fusion of lysosomes to phagosomes and the acidification of the phagosomal lumen. In engulfing cells, UNC-108 is enriched on the surface of phagosomes. We propose that UNC-108 acts on phagosomal surfaces to promote phagosome maturation and suggest that mammalian Rab2 may have a similar function in the degradation of apoptotic cells.
Asunto(s)
Proteínas de Caenorhabditis elegans/fisiología , Caenorhabditis elegans/citología , Proteína de Unión al GTP rab2/fisiología , Secuencia de Aminoácidos , Animales , Apoptosis , Axones/metabolismo , Caenorhabditis elegans/fisiología , Humanos , Lisosomas/fisiología , Datos de Secuencia Molecular , Neuronas/metabolismo , Fagocitos/citología , Fagocitos/fisiología , Fagosomas/fisiología , Mutación Puntual , Alineación de Secuencia , Proteína de Unión al GTP rab2/química , Proteína de Unión al GTP rab2/genéticaRESUMEN
Programmed cell death, or apoptosis, is a genetically controlled process of cell suicide that is a common fate during an animal's life. In metazoans, apoptotic cells are rapidly removed from the body through the process of phagocytosis. Genetic analyses probing the mechanisms controlling the engulfment of apoptotic cells were pioneered in the nematode Caenorhabditis elegans. So far, at least seven genes have been identified that are required for the recognition and engulfment of apoptotic cells and have been shown to function in two partially redundant signaling pathways. Molecular characterization of their gene products has lead to the finding that similar genes act to control the same processes in other organisms, including mammals. In this paper, we review these exciting findings in C. elegans and discuss their implications in understanding the clearance of apoptotic cells in mammals.