Cyclic Nucleotides Protein Phosphorylation And Synaptic Function

While neuroanatomy and neurophysiology were defining the unique features of the synapse as a site for cell to cell signaling in the late fifties, neurochemistry was establishing the identity and studying the biosynthetic pathways of monoamine neurotransmitters. Meanwhile, neuropsychiatry was keeping a vigilant eye on the outcome of this concerted effort with the untold hope that a genetic defect in neurotransmitter metabolism would ac count for the pathogenesis of certain psychiatric ill nesses. Thus, when neurochemists in the early sixties began to study the feasibility of measuring the metabolism of brain neurotransmitters in vivo, clinical biochemists eagerly adopted these methods to their needs and sought to verify whether inborn errors of transmitter biogenesis were a cause for at least certain forms of depression, mania and schizophrenia. Undoubtedly, it is still too early to evaluate the outcome of these studies. However, current opinion holds that gross inborn errors in transmitter metabolism do not anpear to be operative as a primary cause of psychia tric disorders. Though monoamine metabolism appears to be defective in certain groups of psychiatric disorders, the cause of these changes can at best be associated with changes in patterns of neuronal firing. It is generally believed that these persistent changes are determined by a number of unknown factors operative in various psychia tric illnesses. In the attempt to identify the molecular nature of these unknown factors, the focus of current research is directed toward transmitter receptors.

The elucidation of the cellular and molecular bases underlying the inte grated function of the central nervous system, both in disease and in health, must ultimately come from the combined efforts of scientists from many disciplines, including biology, chemistry, histology, pathology, physiology, pharmacology, and psychology. Communication between scientists from these various disciplines-vital to the advancement of our understanding of the function of the nervous system-has become more and more difficult in recent years. Both increasing specialization and the incredible increases in publications pertinent to brain research in a wide spectrum of journals, in symposium volumes, in monographs, in abstracts, and in reviews contrib ute to the problems of cross-communication and even of communication within a scientific discipline. Research on the significance of cyclic nucleo tides to the function of nervous systems is particularly illustrative of the communication problem. Since the initial publications by Sutherland, Rall, and Butcher in the late fifties and early sixties on high levels of adenylate cyclase, phosphodiesterases, and cyclic AMP in brain, the ensuing litera ture of this field has expanded exponentially. At the present time, from five to ten publications relevant to cyclic nucleotides and the nervous system appear each week. Indeed, these are minimal numbers based mainly on examination of literature titles and key index words. Many articles concerned with some aspect of central function contain, buried within their text, experiments with or related to cyclic nucleotides.

Cyclic nucleotides control a number of neuronal properties including neuronal differentiation, pathfinding, regulation of excitability and synaptic transmission, and control of gene expression. Signaling events mediated by cAMP or cGMP are transient and take place within the complex 3-dimensional structure of the neuronal cell. Signaling events happen on the time scale of seconds to minutes and the biological significance of the temporal dimension remains poorly understood. Structural features of neurons (dendritic spines and branches, cell body, nucleus, axon…) as well as AKAPs and other scaffolding proteins that keep signaling enzymes together and form "signaling microdomains", are critical spatial determinants of signal integration. Finally, the types of enzymes involved in signal integration, which are expressed as a number of different types and splice variants, yield another dimension that determines signal integration properties. Biosensor imaging provides direct temporal and spatial measurement of intracellular signals. This novel approach, together with more conventional methods such as biochemistry, electrophysiology, and modeling, now provide a better understanding of the spatial and temporal features of cyclic nucleotide signal integration in living neurons. This topic aims at providing a better understanding of how neurons are "making sense" of cyclic nucleotide signaling in living neurons.

Protein Phosphorylation in Control Mechanisms contains the proceedings of the Miami Winter Symposia entitled ""Protein Phosphorylation in Control Mechanisms,"" held on January 15-16, 1973, in Miami, Florida, and organized by the Department of Biochemistry at the University of Miami School of Medicine. The papers explore the role of protein phosphorylation in control mechanisms, including muscle metabolism and function, cell division, and histone and protamine binding to DNA. This volume is comprised of 28 chapters and begins with an overview of Earl W. Sutherland's scientific work and the involvement of cyclic AMP in enzyme inductions. The discussion then turns to the regulation of muscle metabolism and function by protein phosphorylation; the link between hormonally regulated enzymes in adipose tissue and cyclic AMP-dependent protein kinase; and regulation of the mammalian pyruvate dehydrogenase complex by phosphorylation and dephosphorylation. Subsequent chapters focus on the role of histone phosphorylation in cell division; histone phosphorylation and regulation of nuclear function; and protein phosphorylation in retinal photoreceptors. The final chapter is devoted to acetylation of nuclear proteins in rat testis. This book should be a valuable resource for biochemists.

Showcasing the recent progresses of the field, Cyclic Nucleotide Signaling covers the major tools and methodologies used in various areas of research. The majority of the chapters are protocol oriented, with the goal of providing clear directions for laboratory use. Students and investigators new to the field will find this book particularly informative, as will scientists already actively researching nucleotide signaling.

Volume 54, Symposium S7: Cyclic Nucleotides and Protein Phosphorylation in Cell Regulation documents the proceedings of the 12th Federation of European Biochemical Societies (FEBS) Meeting held in Dresden, Germany on July 5-7, 1978. This book discusses the biological significance and biochemical aspects of cyclic nucleotides and protein phosphorylation in cell regulation. The general aspects of cyclic nucleotide metabolism and action; cyclic nucleotides and nervous system; and cyclic nucleotides in muscle tissues are also elaborated. This publication likewise covers the cyclic nucleotides in secretion processes and miscellaneous aspects of cyclic nucleotide-dependent and independent protein phosphorylation. This volume is valuable to biochemists and biologists concerned with the cyclic nucleotides and protein phosphorylation in cell regulation.