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Vol. 15, Issue 2, 861-869, February 2004

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Involvement of the AP-1 Adaptor Complex in Early Steps of Phagocytosis and Macropinocytosis

Yaya Lefkir ^*, Marilyne Malbouyres ^*, Daniel Gotthardt , Adrian Ozinsky , Sophie Cornillon , Franz Bruckert ^||, Alan A. Aderem , Thierry Soldati ^¶, Pierre Cosson , and François Letourneur ^* ¶ 

^* Institut de Biologie et Chimie des Protéines, UMR5086-CNRS/Université Lyon I, IFR 128 BioSciences Lyon-Gerland, 69367 Lyon, France; Department of Molecular Cell Research, Max-Planck-Institute for Medical Research, D-69120 Heidelberg, Germany; Institute for Systems Biology, Seattle, Washington 98105; Université de Genève, Centre Médical Universitaire, Département de Morphologie, CH-1211 Genève, Switzerland; ^|| Laboratoire de Biochimie et Biophysique de Systémes Intégrés, 38054 Grenoble, France; and ^¶ Department of Biological Sciences, Imperial College of Science Technology and Medicine, London SW7 2AZ, United Kingdom

Submitted June 6, 2003; Revised September 5, 2003; Accepted October 15, 2003
Monitoring Editor: Peter Devreotes

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.

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

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