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First published online 27 January 2009
doi: 10.1242/jcs.038521
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Research Article |
1 Department of Cell Research and Immunology, Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, 69978, Israel
2 Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv, 69978, Israel
3 Howard Hughes Medical Institute, Strang Laboratory of Cancer Research, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
4 Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel
* Author for correspondence (e-mail: horwitzm{at}post.tau.ac.il)
Accepted 23 October 2008
Endocytosis, which is a key process in eukaryotic cells, has a central role in maintaining cellular homeostasis, nutrient uptake, development and downregulation of signal transduction. This complex process depends on several protein-protein interactions mediated by specific modules. One such module is the EH domain. The EH-domain-containing proteins comprise a family that includes four vertebrate members (EHD1-EHD4) and one Drosophila ortholog, Past1. We used Drosophila as a model to understand the physiological role of this family of proteins. We observed that the two predicted Past1 transcripts are differentially expressed both temporally and spatially during the life cycle of the fly. Endogenous Past1 as well as Past1A and Past1B, expressed from plasmids, were localized mainly to the membrane of Drosophila-derived cells. We generated mutants in the Past1 gene by excising a P-element inserted in it. The Past1 mutants reached adulthood but died precociously. They were temperature sensitive and infertile because of lesions in the reproductive system. Garland cells that originated from Past1 mutants exhibited a marked decrease in their ability to endocytose fluorescently labeled avidin. Genetic interaction was found between Past1 and members of the Notch signaling pathway, suggesting a role for Past1 in this developmentally crucial signaling pathway.
Key words: Past1, Drosophila, EHD, EH domain, Endocytosis
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