Molecular Neurobiology

This book is a collection of papers describing some of the first attempts to apply the techniques of recombinant DNA and molecular biology to studies of the nervous system. We believe this is an important new direction for brain research that will eventually lead to insights not pos sible with more traditional approaches. At first glance, the marriage of molecular biology to brain research seems an unlikely one because of the tremendous disparity in the histories of these two disciplines and the problems they face. Molecular biology is by nature a reductionist approach to biology. Molecular biologists have always tried to attack central questions in the most direct approach possible, usually in the most simple system available: a bacterium or a bacterial virus. Important experiments can usually be repeated quickly and cheaply, in many cases by the latest group of graduate students entering the field. The success of molecular biology has been so profound because the result of each important experiment has made the next critical question obvious, and usually answerable, in short order. Studies of the nervous system have a very different history. First, the human brain is what really interests us and it is the most complex structure that we know in biology. The central question is clear: How do we carry out higher functions such as learning and thinking? How ever, at present there is no widely accepted and testable theory of learn ing and no clear path to such a theory.

Contenu

1. The Molecular Biology of the Na,K-ATPase and Other Genes Involved in the Ouabain-Resistant Phenotype.- 1. Introduction.- 2. Molecular Cloning of the Na,K-ATPase Catalytic Subunit.- 3. Organization and Expression of the Rat Sodium Pump a-Subunit Gene.- 4. Organization and Expression of the a-Subunit Gene in Ouabain-Resistant Cell Lines.- 5. Isolation and Characterization of a Ouabain-Resistance Gene.- 6. Transfer of the Sodium Pump a-Subunit Gene Confers Ouabain Resistance to Ouabain-Sensitive Cells.- 7. Isolation of Genes Related to the Sodium Pump and Their Expression in a Ouabain-Resistant Cell Line.- 8. Conclusions and Future Prospects.- References.- 2. Molecular Biology of the Genes Encoding the Major Myelin Proteins.- 1. Introduction.- 2. Formation and Structure of the Myelin Sheath.- 3. Myelin-Specific Proteins.- 4. Conclusion.- References.- 3. Molecular Biology of the Neural and Muscle Nicotinic Acetylcholine Receptors.- 1. Introduction.- 2. Isolation of cDNA Clones Coding for the Acetylcholine Receptor Expressed in the Torpedo Electric Organ.- 3. Isolation of cDNA Clones Coding for Mouse Skeletal Muscle Acetylcholine Receptor.- 4. Structure of the Acetylcholine Receptor.- 5. Expression of the Acetylcholine Receptor Genes in Skeletal Muscle.- 6. Brain Receptors.- 7. Conclusion.- References.- 4. Molecular Biology of Muscle Development: The Myosin Gene Family of Caenorhabditis elegans.- 1. Introduction.- 2. Genetics of the unc-54 Locus.- 3. Immunological Identification and Localization of Myosin Isoforms.- 4. Molecular Cloning of the unc-54 and myo-1,2,3 MHC Genes.- 5. Immunological Identification of the Products of the myo-1,2,3 MHC Genes.- 6. Structural Organization of the Nematode MHC Genes.- 7. Molecular Anatomy of the Myosin Molecule.- 8. Sequences and Molecular Interpretation of unc-54 Mutations.- 9. Myosin Protein Expression and Mutagenesis in E. coli.- References.- 5. Small Cardioactive Peptides in A and B: Chemical Messengers in the Aplysia Nervous System.- 1. Introduction.- 2. The Distribution of SCP-Immunoreactive Neurons in the CNS.- 3. The SCP Gene and Precursor Protein.- 4. SCP Gene Expression.- 5. Subcellular Localization.- 6. Coexistence of Multiple Transmitters.- 7. Physiological Activities.- 8. Conclusions.- References.- 6. Molecular Biology Approach to the Expression and Properties of Mammalian Cholinesterases.- 1. Introduction: Expression of Cholinesterases as a Research SubjectScientific Significance, Advantages, and Difficulties.- 2. Expression of Cholinesterase mRNAs in Microinjected Xenopus Oocytes.- 3. Identification of Drosophila DNA Fragment that Hybridizes with Cholinesterase mRNA.- 4. Isolation and Partial Characterization of Human DNA Fragments Homologous to DroSR.- 5. Preparation of Synthetic Oligonucleotide Probes According to the Consensus Sequence at the Organophosphate-Binding Site.- 6. Preliminary Characterization of Neuroche cDNA Clones.- 7. Summary and Conclusions.- References.- 7. Genes and Gene Families Related to Immunoglobulin Genes.- 1. Introduction.- 2. Immunoglobulin Genes and the Immunoglobulin Domain.- 3. The T-Lymphocyte Cell-Surface Receptor for Antigen.- 4. Class I MHC Genes.- 5. Class II MHC Genes.- 6. Cell-Surface Receptors for Transepithelial Transport of Immunoglobulin.- 7. The T-Cell Accessory Molecules T4 and T8.- 8. Related Members of the Immunoglobulin Supergene Family Expressed in the Nervous System.- 9. Conclusion: The Evolution of the Immunoglobulin Super family..- References.- 8. Specificity of Prohormone Processing: The Promise of Molecular Biology.- 1.Introduction.- 2. Gene-Transfer Systems.- 3. Enzymatic Studies.- 4. The Internal Environment of Secretory Granules.- 5. Perspectives.- References.