(Director: Pierre J. COURTOY) Two years after its first gathering in Oeiras, Portugal, the European Endocytosis Group convened for a second workshop at the Pasteur Institute, Paris, on October 1-5, 1990. The meeting is reported in detail in this volume; a preliminary coverage, based on the overviews of each session, has appeared in the New Biologist (1991, 3:243-252). The three main objectives, to broaden the audience, to present a more comprehensive view of the multiple aspects of endocytosis, from basic biology to health, disease and therapy, as well as to clarify controversial issues, have been largely fulfilled. The Second European Workshop on Endocytosis was attended by more than tOO participants, originating from 18 countries. 59 lectures and 35 posters were presented. In addition, vivi~ roundtables allowed to thoroughly discuss the dynamics and the regulation of the endocytic apparatus, as well as the role of endocytosis in antigen presentation. Endocytosis is a general and distinctive property of all eukaryotic cells, including protists, plants and fungi.

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This book provides an updated and comprehensive view ofbasic and applied aspects of endocytosis.The first section covers new developments obtained bymolecular tracking of defined probes in microcinematographyand high-resolution electronmicroscopy, new procedures incell fractionation, cell-free assays and genetic engineeringof receptors transfected into eucaryotic cells. It alsodescribes endocytosis in non-mammalian cells.The second section explores several applications to theunderstanding of health and disease, especially in theimmune response and the relations between cells andintracellular pathogens, including in immunodeficientpatients. It also discusses toxins and explorestheirpotential for immunotoxins, as well as the development ofbetter designed drugs.

Inhalt
I. Structure, Dynamics and Functions of the Endocytic Apparatus.- 1.1. Surface events. Mobility and clustering.- . Dynamic cytomatrix-membrane interactions investigated with Nanovid microscopy.- Analysis of receptor dynamics, as studied with surface replicas.- Surface distribution and pathway of internalization of C3b receptors (CR1) in human neutrophils.- 1.2. Clathrin-coated pits and clathrin-independent endocytosis.- The dynamics of clathrin coats in living cells measured by advanced fluorescence microscopy.- Assembly proteins and adaptors in clathrin-coated vesicles.- Molecular biology of the adaptins.- Clathrin-independent endocytosis.- 1.3. Dynamics of endosomes.- New insights into the endocytic pathway.- The compartments of the endocytic pathway.- Protein exchange within the lysosome and the pre-lysosome compartment. A mechanism for maintaining organelle functionality ?.- Endosomal pH regulation and the maturation model for lysosome biogenesis.- 1.4. Cell-free analysis of endocytic traffic.- Effect of ATP?S on the formation of coated vesicles in broken HeLa cells.- ATP is required for receptor-mediated endocytosis both in vivo and in vitro.- Regulation of endocytic membrane traffic.- The interaction of late endosomes with lysosomes in a cell-free system.- Roundtable. Cell-free systems.- 1.5. Molecular processing by endosomes.- Regulation of ATP-dependent endosome acidification.- Degradation of insulin and glucagon in isolated liver endosomes. Functional relationships with ATP-dependent endosomal acidification and partial characterization of degradation products.- Signaling of receptor tyrosine kinases across the endosomal membrane.- 1.6. Recycling pathways.- Membrane recycling in the epithelium of seminal vesicle intersects the secretory pathway.- Endocyticpathways.- Intracellular traffic of the growth factor interleukin-2 and its receptors in human T lymphocytes.- Two recycling pathways of epidermal growth factor-receptor complexes in A431 cells.- Oligosaccharide reprocessing of plasma membrane glycoproteins.- 1.7. Biogenesis of lysosomes.- Lysosomal enzyme transport between Golgi and endosomes.- The nineteen amino acid-cytoplasmic tail of lysosomal acid phosphatase contains an endocytosis signal necessary and sufficient for targeting to lysosomes.- Biochemical characterization, structure and transport of lysosomal integral membrane proteins.- Mannose phosphate-independent membrane association of lysosomal enzymes occurs after passage of the Golgi complex.- 1.8. Heterogeneity of lysosomes and autophagy.- LGP10D10, a lysosomal membrane protein.- Receptor-mediated endocytosis in liver endothelial cells. Evidence of lysosomal heterogeneity.- Autophagic-endocytic interactions in hepatocytes.- 1.9. The biogenesis of epithelial polarity.- Plasma membrane biogenesis and vesicle traffic in polarized hepatocytes. What can perturbations tell us ?.- Plasma membrane polarity of rat hepatocytes in primary culture.- Sorting of endogenous proteins in intestinal epithelial cells.- Lipid sorting by the formation of microdomains of sphingolipids. A model and its consequences.- 1.10. Transcytosis.- Analytical subcellular fractionation of receptor-mediated transcytosis in rat hepatocytes.- Temperature dependence of transcytotic pathways in rat liver.- Fc receptor-mediated endocytosis in polarized and nonpolarized cells.- Endocytosis in MDCK cells.- Protein handling from apical and basolateral surfaces in rat and rabbit renal proximal tubules.- II. Endocytosis in Health, Disease and Therapy.- 2.1. Endocytosis in the immune response.- Antigen processing in B lymphocytes.- Endocytosis and biosynthetic transport of murine MHC class II molecules in antigen-presenting cells.- Endocytosis. Molecular mechanism and role in the immune response.- Endocytosis of CD4 in lymphoid and non-lymphoid cells.- Role of transepithelial transport in triggering a mucosal immune response and in delivery of mucosal antibodies into secretions.- 2.2. Phagocytosis and intracellular pathogens.- Overview on the relations of pathogenic microorganisms with their host cell.- Intracellular growth of Mycobacterium avium in macrophages. Consequences on membrane traffic and exchange of contents between endosomes, lysosomes and phagosomes.- Morphology, composition and functions of the endocytic compartment housing Leishmania amazonensis in infected macrophages.- Entry into eukaryotic cells and intracellular movement of Shigella flexneri.- 2.3. Entry of viruses and toxins.- On the role of endocytosis in the entry of animal viruses.- Endocytic uptake of ricin and shiga toxin.- Endocytosis of Clostridium spiroforme binary toxin by Hep2 cells.- 2.4. Lysosomal diseases.- Correlation between residual activity of a lysosomal hydrolase and the severity of the resulting storage disease.- Lysosomes as suicide bags.- Lysosomal storage disorders and toxicity induced by aminoglycoside antibiotics and polyanionic peptides.- 2.5. Endocytosis in non-mammalian cells.- Endocytosis in the emergence of eukaryotic life.- Endocytosis in plants. Problems and perspectives.- Receptor-mediated endocytosis of ?-factor by Saccharomyces cerevisiae a cells.- Receptor-mediated endocytosis in Trypanosoma brucei.- 2.6. Endocytosis and drug targeting.- Lysosomes of Leishmania mexicana sp. as targets for potential therapeutic agents.- Glycosylated polymers as carriers fortargeting antiviral and antiparasite drugs.- Immunotoxins.- Directory of participants.