Biomembranes. A Multi-Volume Treatise Series

Progress in understanding the nature of the biological membrane has been very rapid over a broad front, but still pockets of ignorance remain. Application of the techniques of molecular biology has provided the sequences of a very large number of membrane proteins, and has led to the discovery of superfamilies of membrane proteins of related structure. In turn, the identification of these superfamilies has led to new ways of thinking about membrane processes. Many of these processes can now be discussed in molecular terms, and unexpected relationships between apparently unrelated phenomena are bringing a new unity to the study of biological membranes. The quantity of information available about membrane proteins is now too large for any one person to be familiar with anything but a very small part of the primary literature. A series of volumes concentrating on molecular aspects of biological membranes therefore seems timely. The hope is that, when complete, these volumes will provide a convenient introduction to the study of a wide range of membrane functions. This first volume is devoted to general surveys of the structure and synthesis of membrane proteins and lipids, of the interactions between lipids and proteins, and of the functions of biological membranes.

Volume 3 of Biomembranes covers receptors of cell adhesion and cellular recognition. Proteins in the plasma membrane of cells are heavily involved in processes of cell adhesion, but such proteins were not actually isolated and characterized until the mid-1970s. Since then, application of the methods of molecular biology has led to the recognition of four major classes of cell adhesion molecule (CAMs), the immunoglobulin super family, the cadherins, the integrins, and the selecting. A convenient system in which to study the importance of cell adhesion is in blood platelets where aggregation eventually leads to thrombus formation in a process involving a range of surface glycoproteins. Interaction with the extracellular matrix is exemplified by CD44, the receptor for hyaluronan, and a complex carbohydrate that is a major component of the extracellular matrix surrounding migrating and proliferating cells. Membrane-associated mucins have a variety of effects on cell adhesion. The super family of immunoglobulin related proteins also include the T cell receptors and the major histocompatibility complex (MHC), which, together with the receptors for immunoglobulins (the Fc receptors), are of fundamental importance in the processes of immunity. Volume 3 of Biomembranes explores the structures and functions of the molecules involved in these important functions of the cell.

Volume 4 of Biomembranes covers endocytosis, exocytosis and related processes. A major role of the plasma membrane is as a permeability barrier, keeping the inside of the cell inside and the outside, outside. Mechanisms must then exist to allow movement of material between the cell and its environment. One mechanism for export from the cell is by exocytosis, a process in which the membranes of secretory vesicles fuse with the plasma membrane releasing the contents of the vesicle into the extracellular medium. The process has been studied in particular depth for the release of neurotransmitters at the synapse. Import into the cell is possible by the process of receptor-mediated endocytosis in which selected plasma membrane proteins are internalizes; when these proteins are receptors for macromolecules, the result is uptake of the macromolecule. Transferring, the low-density lipoprotein, and asialoglycoproteins are all taken up into cells in this way. Phagocytosis, the ingestion of cells and cell fragments by neutrophils and macrophages, also involves receptors - on the phagocytic membrane - of which the best studied are those for the Fc domain of IgG, for the third component of complement, and for the mannose/fructose carbohydrates. Protection of a host against infection can also be achieved by damaging the integrity of the plasma membrane of the invading organism. This is the strategy evolved by the cytotoxic T lymphocytes, which produce a pore-forming toxin, perforin. Volume 4 of Biomembranes explores the structures and mechanisms involved in these biologically and medically important processes.

Volume 5 of Biomembranes covers an important group of membrane proteins, the ATPases. The P-type ATPases couple the hydrolysis of ATP to the movement of ions across a membrane and are characterized by the formation of a phosphoyrlated intermediate. Included are the plasma membrane and muscle sarcoplasmic reticulum Ca2+ -ATPases, the (Na+ -K+) -ATPase, the gastric (H+ -K+) -ATPase, the plasma membrane H+ -ATPase of fungi and plants, the Mg2+ - transport ATPase, the Salmonella typhimurium, and the K+ -ATPase of Escherichia coli, KdpB. The other important classes of ATPase in eukaryotic systems are the vacuolar H+ -ATPases and the F0F1 ATP synthase, and, in bacteria, the anion-translocating ATPases, responsible for resistance to arsenicals and antimonials, and the (Na+ -Mg2+) -ATPase of Acholeplasma. Finally, eukaryotic systems contain a variety of ectonucleotidases important, for example, in hydrolysis of extracellular ATP released as a cotransmitter from cholinergic and adrenergic nerve terminals. Volume 5 of Biomembranes explores structure-function relationships for these mebrane-bound ATPases.

Volume 6 of Biomembranes covers transmembrane receptors and channels. A particularly important role for the membrane is that of passing messages between a cell and its environment. Part I of this volume covers receptors for hormones and growth factors. Here, as in so many other areas of cell biology, the application of the methods of molecular biology have led to the recognition of a number of families of receptors. Typically, such receptors contain an extracellular ligand binding domain, a transmembrane domain, and an intracellular catalytic domain whose activation, as a result of ligand binding, leads to generation of second messengers within the cell and stimulation of a range of cytosolic enzymes. An alternative signaling strategy, exploited in particular in the nervous system, is to use ion channels to allow controlled movement of monovalent (Na+, K+) or divalent (Ca2+) cations in or out of the cell, resulting in changes in membrane potential or alterations in the intracellular concentration of Ca2+. Part II of this volume is concerned with these ion channels and with other, often simpler, ion channel systems whose study can throw light on channel mechanism.