Advances in Cellular and Molecular Biology of Membranes and Organelles – serie

The present volume focuses on microbial invasion strategies of pathogen uptake. An accompanying volume (Vol. 5) in the series presents the phagocytic process from the viewpiont of the host cell. This field of study is growing rapidly after a somewhat slow start over recent decades. This collection of invited chapters attempts to reflect current research and brings together cell biologists, microbiologists, and immunologists wiht disthemes, hopefully like a symphony rather than a boring catalogue. It will be evident that editorial bias favors intracellular parasitism and medically important organisms. The neutrophil is far more than a supporting player to the macrophage and some attempt is made to remind the reader of some of its unique skills. To retain a manageable size, the emphasis is on relatively early events such as mutual recognition, cell entry, and response, rather than on longterm changes in gene expression by either host cell or pahtogen. Viruses are excluded not because of lack of importance but because of somewhat different research approaches, although it is becoming increasingly clear that large viruses (e.g. Vaccinia) and Listeria monocytogenes, share common strategies in invasion and intercellular spread.

The intent in initiating this volume was to bring together a series of essays which would define our present understanding of the endosome and lysosome and their interrelationship. The editors deliberately encouraged the contributors to be speculative; to strive to put order to the "real" world of incomplete and sometimes conflicting data. Seeing science from the laboratory bench can often be like viewing an impressionistic painting from up close; a series of paint dabs with no apparent order. The contributors to this volume were asked to step back and leave the reader with a sense of the whole as well as the detail. To the extent that this has happened, the credit should go to the individual authors. Our understanding of endosomes and lysosomes has undergone a molecular revolution over the last decade. Hence, we now know much about the molecular features required for internalization of an endocytic receptor, or the function of mannose 6-phosphate receptors in the transport of lysosomal enzymes. We can trace and follow the flow of molecules. In this volume current molecular knowledge concerning the function and relationship of endosomes and lysosomes is presented. Because of this vast increase in knowledge of molecules, we have realized that endosomes in particular are very ephemeral organelles. In fact, endosomes may well not be discrete entities but rather continuously changing and evolving in their molecular composition. The dynamic nature of the relationship between endosomes and lysosomes is the unifying focus of the genetic, biochemical, microscopic, and molecular biological approaches described in the chapters which follow.

Membranes are highly dynamic and operate not only as inert boundaries, but the packages they carry around in a cell are well addressed fro appropriate delivery. This holds for a variety of endomembrane systems engaged in exo- and endocytosis, for organelles along the biosynthetic pathway, phagosomes, and lysosomes. It also holds for the establishment of functional surface properties. Cell pairing (conjugation) phenomena are a good model for the problem of how a cell can discriminate between "self" and "non-self". On the other hand parasitic sporozoa developed to experts in masking their molecular sur-"face"by frequent shedding of their variant antigens. The discovery of their glycosyl-phosphatidylinositol (GPI) anchor has led to the discovery, in polar epithelial cells, of a specific targeting mechanism for GPI-anchored surface glycoproteins. Over one hundred such proteins have been detected in metazoans since then.Many of these basic aspects are dealt with in this book using quite different methodical approaches. Of course, there are many more aspects previously known from metazoan systems and such aspects then had to be verified also for Protozoa systems and such aspects then had to be verified also for protozoa. In this context, it is fascinating to see how basic cellular functions are maintained - with variations of the basic theme - throughout evolution.However, sometimes cell biologists dedicated to work with protozoa have to live with a regrettable phenomenon. Colleagues working with "higher" eukaryotic cells are frequently unaware of the fact that the primary input may have come from work with protozoa. Some phenomena may even be rediscovered inadvertently. In this sense, this book should address not only colleagues working with protozoa but also many of our fellow cell biologists working with metazoan cells.

The incentive for putting together Volume 4 of this series was to review the wealth of new information that has become available in prokaryotic organisms in protein export and membrane biogenesis. Just in the last several years, protein translocation has now been efficiently reconstituted using defined components and the mechanism by which proteins are moved across membrane bilayers is now being examined at a higher resolution. In addition, because of a new technical breakthrough using osmolytes, it is now possible to reconstitute a number of channel proteins, ATPase, receptors, and transporters. In many cases, it is possible to successfully predict the membrane topology of these types of proteins using both "hydrophobicity analysis" and the "positive inside" rule. In this volume, two chapters focus on protein translocation across membranes (Biochemical Analyses of Components Comprising the Protein Translocation Machinery of E. Coli; Protein Translocation Genetics), while several others on how proteins assemble into the ineer membrane of E. Coli (Membrane Protein Assembly; Membrane Insertion of Small Proteins: Evolutionary and Functional Aspects; Pigment-Protein Complex Assembly in Rhodobacter sphaeroides and Rhodobacter Capsulatus). Other sections review recent progress on transporters (Identification and Reconstitution of Anion Exchange Mechanisms in Bacteria; Helic Packing in the C-Terminal Half of Lactose Permease) and signal transduction (Mechanism of Transmembrane Signaling in Osmoregulation) as well as the assembly of prints into the outer membrane (Export and Assembly of Outer Membrane Proteins in E. coli). Although the emphasis of the book is on proteins, the role of phospholipids in controlling various cell surface processes is reviewed (Role of Phospholipids in coli Cell Function). I should point out the reason for the rapid progress in bacteria research is because of the possibility to apply biochemistry and genetics in this organism.