Sigma 1- and mu 1-Adaptin homologues of Leishmania mexicana are required for parasite survival in the infected host.
The sorting of membrane-bound proteins from the trans-Golgi network to lysosomal/endosomal compartments is achieved by preferential inclusion into clathrin-coated vesicles. Contained within the cytoplasmic domains of such proteins, specific sequence motifs have been identified (tyrosine-based and/or di-leucine-based) that are essential for targeting and are recognized by a family of heterotetrameric adaptor complexes, which then recruit clathrin. These cytosolic protein complexes, which have been found in a wide variety of higher eukaryotic organisms, are essential for the development of multicellular organisms. In trypanosomatids, the adaptin-mediated sorting of proteins is largely uncharacterized. In order to identify components of the adaptor-complex machinery, this study reports the cloning and characterization of sigma 1- and mu 1-adaptin gene homologues from the eukaryotic protozoan parasite, Leishmania mexicana. Generation of sigma 1- and mu 1-adaptin gene deletion mutants shows that these promastigote parasites are viable in culture, but are unable to establish infection of macrophages or mice, indicating that adaptin function is crucial for pathogenesis in these unicellular organisms.
Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, Corrensstrasse 38, D-72076 Tübingen, Germany. sg360@cam.ac.uk
Suzanne
S
Gokool
D033983:Adaptor Protein Complex mu Subunits / Q000502:physiology*; D034002:Adaptor Protein Complex sigma Subunits / Q000502:physiology*; D000483:Alleles; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D015139:Blotting, Southern; D015153:Blotting, Western; D017173:Caenorhabditis elegans; D003001:Cloning, Molecular; D003593:Cytoplasm / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004331:Drosophila melanogaster; D004587:Electrophoresis, Agar Gel; D011992:Endosomes / Q000378:metabolism; D017353:Gene Deletion; D005816:Genetic Complementation Test; D007894:Leishmania mexicana / Q000472:pathogenicity* / Q000502:physiology; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D010537:Peritoneum / Q000166:cytology; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014162:Transfection; D021601:trans-Golgi Network
D033983:Adaptor Protein Complex mu Subunits; D034002:Adaptor Protein Complex sigma Subunits; D004247:DNA