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MBC in Press, published online ahead of print November 14, 2003
Mol. Biol. Cell 10.1091/mbc.E03-06-0365

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Submitted on June 6, 2003
Revised on September 5, 2003
Accepted on October 15, 2003

Involvement of the AP-1 adaptor complex in early steps of phagocytosis and macropinocytosis

Yaya Lefkir1, Marilyne Malbouyres1, Daniel Gotthardt2, Adrian Ozinsky3, Sophie Cornillon4, Franz Bruckert5, Alan A. Aderem3, Thierry Soldati6, Pierre Cosson4, and François Letourneur1*

1 Institut de Biologie et Chimie des Protéines, UMR5086 - CNRS/Université Lyon I, IFR 128 BioSciences Lyon-Gerland, 7 Passage du Vercors, 69367 Lyon cedex 07, France
2 Department of Molecular Cell Research, Max-Planck-Institute for Medical Research, Jahnstrasse 29, D-69120 Heidelberg, Germany
3 Institute for Systems Biology, 4225 Roosevelt Way NE, Seattle WA 98105, USA
4 Université de Genève, Centre Médical Universitaire, Département de Morphologie, CH-1211 Genève 4, Switzerland
5 Laboratoire de Biochimie et Biophysique des Systémes Intégrés, 38054 Grenoble Cedex 9, France
6 Department of Biological Sciences, Imperial College of Science Technology and Medicine, London SW7 2AZ, United Kingdom

* Corresponding author. E-mail address: f.letourneur{at}ibcp.fr.

The best described function of the adaptor complex-1 (AP-1) is to participate in the budding of clathrin-coated vesicles from the trans-Golgi network and endosomes. Here we show that AP-1 is also localized to phagocytic cups in murine macrophages as well as in Dictyostelium amoebae. AP-1 is recruited to phagosomal membranes at this early stage of phagosome formation and rapidly dissociates from maturing phagosomes. To establish the role of AP-1 in phagocytosis, we made used of Dictyostelium mutant cells (apm1- cells) disrupted for AP-1 medium chain. In this mutant, phagocytosis drops by 60% indicating that AP-1 is necessary for efficient phagocytosis. Furthermore, phagocytosis in apm1- cells is more affected for large rather than small particles and cells exhibiting incomplete engulfment are then often observed. This suggests that AP-1 could participate in the extension of the phagocytic cup. Interestingly, macropinocytosis, a process dedicated to fluid-phase endocytosis and related to phagocytosis, is also impaired in apm1- cells. In summary, our data suggest a new role of AP-1 at an early stage of phagosome and macropinosome formation.




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