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J. Biol. Chem., Vol. 278, Issue 32, 29400-29409, August 8, 2003

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1- and µ1-Adaptin Homologues of Leishmania mexicana Are Required for Parasite Survival in the Infected Host^*

Suzanne Gokool 

From the Max-Planck-Institut für Biologie, Abteilung Membranbiochemie, Corrensstrasse 38, D-72076 Tübingen, Germany

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 1- and µ1-adaptin gene homologues from the eukaryotic protozoan parasite, Leishmania mexicana. Generation of 1- and µ1-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.

Received for publication, May 1, 2003

^* This research was funded by the Max-Planck-Gesellschaft. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. The nucleotide sequence(s) reported in this paper has been submitted to the GenBank^TM/EBI Data Bank with accession number(s) AF514805 and AF514806.

To whom correspondence should be addressed: Cambridge Institute for Medical Research, Wellcome Trust/MRC Bldg., Box 139, Addenbrooke's Hospital, Hills Rd., Cambridge CB2 2XY, United Kingdom. E-mail: sg360{at}cam.ac.uk.

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