Chapter 1/Cytology and Organization of Cell Types 7 dependent for both import and export. The enzyme 2.2.1. PROTEINS SYNTHESIZED BY NEURONS GTPase or Ran provides energy and cycles between FOR ExPORT a guanosine triphosphate(GTP)- and guanosine Appreciation of the tremendous protein synthetic diphosphate (GDP)-bound state, with Ran GTP nerve being primarily nuclear and Ran GDP primarily tions is relatively recent. Neuronal form and mem- cytoplasmic in location. Small molecules(less than brane properties were the main focus of earlier 40 kDa), ions, and metabolites can cross the nuclear neurobiologists. However, the compelling discovery pore complex by passive diffusion. Some proteins of glandular cells in the spinal cord of fish by Carl th the are thought to be imported both passively and , peidel in 1919 and of neurosecretory cells in the hypothalamus by Ernst Scharrer in 1928 directed actively. Some particles, such as the assembled attention to the great degree of biosynthetic activity mature ribosomes, are too large to gain entrance in the perikaryon. Ernst Scharrer noticed that the through these passageways, ensuring that protein secretory activity of diencephalic neurons was com- synthesis is restricted to the cytoplasm. parable with that seen in endocrine cells. This obser 2.1. 4. DYNAMIC NUCLEAR MORPHOLOGY REFLECTS vation stimulated further interest in finding structural ALTERATIONS IN THE GENOME counterparts of the secretory process in neurons. The mechanisms involved in peptide biosynthesis and Although nuclear events occur on a molecular scale, posttranslational processing are now well-known they may be detected by gross adjustments in nuclear Related molecular and biochemical events are morphology. The overall size and shape of nuclei and detailed in other chapters of this volume. In this nucleoli can change with the metabolic and physiolo- chapter, we describe the structural correlates of demands of the neuron. Depending on transcrip- these functions as they occur in various parts of the tional activity, various segments of the chromatin can nerve cell condense or decondense. resulting in a relative change in the disposition of heterochromatin and euchromatin and altering the general appearance of 2. 2.1.1. Synthesis of Exportable Neuropeptides the nucleus. For example, in the hypothalamus, a on the Rough Endoplasmic Reticulum. Neurons brain area controlling female reproductive behavior. must transmit chemical information and electrical the gonadal steroid hormone estrogen exerts a pro- signals over very long distances. Proteins are synthe found influence on nuclear mophology, altering the sized, packaged, processed, stored, and released in size, shape, and position of heterochromatic regions. difterent domains of the neuron. The synthesis of Nucleolar size is also subject to the physiologic con- bosomal subunits produced in the nucleolus enter the ditions of the cell. Estrogen treatment has a pro nounced effect on precursor ribosomal RNA levels. cytoplasm, where they are assembled and activated to hich are accompanied by a significant increase in form functional ribosomes. In some cases, they attach nucleolar area in the hypothalamus of ovariecto- to membranous cisternae comprising the rough endo- mized animals. Nucleolar hypertrophy Is Followed plasmic reticulum(Fig. 4). The outer nuclear mem- by a massive increase in rough endoplasmic reticulum brane ramifies within the cytoplasm as it encircles the in these neurons nucleus and studded with ribosomes. also becomes part of the protein synthetic apparatus Messenger rnas associated with ribosomes are 2.2. Neurons Are Actively Engaged in Protein translated into precursor proteins. The precursors Synthesis are larger than the biologically active peptides and Information contained within the genome is must be enzymatically cleaved and modified to attain expressed as biologically active peptides in the cell their final form Instructions about whether a given body or perikaryon of the neuron. Some peptides protein is destined for export are also encoded in the are neuron specific, such as some of the neurosecre- DNA of its precursor. A portion of the complemen tory peptides, cytoskeletal proteins, ion channels, and tary messenger RNa is translated into a signal pep- receptors. Others are common to all cells and are tide, which directs ribosomes to the cisternae of the involved in increasing the efficiency of transcriptional rough endoplasmic reticulum. Peptides lacking a and translational events related to the production, signal sequence cannot gain entry to the cisternae transport, and release of these proteins The disposition and extent of rough endoplasmicdependent for both import and export. The enzyme GTPase or Ran provides energy and cycles between a guanosine triphosphate (GTP)- and guanosine diphosphate (GDP)-bound state, with Ran GTP being primarily nuclear and Ran GDP primarily cytoplasmic in location. Small molecules (less than 40 kDa), ions, and metabolites can cross the nuclear pore complex by passive diffusion. Some proteins associated with the inner nuclear membrane itself are thought to be imported both passively and actively. Some particles, such as the assembled mature ribosomes, are too large to gain entrance through these passageways, ensuring that protein synthesis is restricted to the cytoplasm. 2.1.4. DYNAMIC NUCLEAR MORPHOLOGY REFLECTS ALTERATIONS IN THE GENOME Although nuclear events occur on a molecular scale, they may be detected by gross adjustments in nuclear morphology. The overall size and shape of nuclei and nucleoli can change with the metabolic and physiolo￾gic demands of the neuron. Depending on transcrip￾tional activity, various segments of the chromatin can condense or decondense, resulting in a relative change in the disposition of heterochromatin and euchromatin and altering the general appearance of the nucleus. For example, in the hypothalamus, a brain area controlling female reproductive behavior, the gonadal steroid hormone estrogen exerts a pro￾found influence on nuclear morphology, altering the size, shape, and position of heterochromatic regions. Nucleolar size is also subject to the physiologic con￾ditions of the cell. Estrogen treatment has a pro￾nounced effect on precursor ribosomal RNA levels, which are accompanied by a significant increase in nucleolar area in the hypothalamus of ovariecto￾mized animals. Nucleolar hypertrophy is followed by a massive increase in rough endoplasmic reticulum in these neurons. 2.2. Neurons Are Actively Engaged in Protein Synthesis Information contained within the genome is expressed as biologically active peptides in the cell body or perikaryon of the neuron. Some peptides are neuron specific, such as some of the neurosecre￾tory peptides, cytoskeletal proteins, ion channels, and receptors. Others are common to all cells and are involved in increasing the efficiency of transcriptional and translational events related to the production, transport, and release of these proteins. 2.2.1. PROTEINS SYNTHESIZED BY NEURONS FOR EXPORT Appreciation of the tremendous protein synthetic activity of the nerve cell and its functional implica￾tions is relatively recent. Neuronal form and mem￾brane properties were the main focus of earlier neurobiologists. However, the compelling discovery of glandular cells in the spinal cord of fish by Carl Speidel in 1919 and of neurosecretory cells in the hypothalamus by Ernst Scharrer in 1928 directed attention to the great degree of biosynthetic activity in the perikaryon. Ernst Scharrer noticed that the secretory activity of diencephalic neurons was com￾parable with that seen in endocrine cells. This obser￾vation stimulated further interest in finding structural counterparts of the secretory process in neurons. The mechanisms involved in peptide biosynthesis and posttranslational processing are now well-known. Related molecular and biochemical events are detailed in other chapters of this volume. In this chapter, we describe the structural correlates of these functions as they occur in various parts of the nerve cell. 2.2.1.1. Synthesis of Exportable Neuropeptides on the Rough Endoplasmic Reticulum. Neurons must transmit chemical information and electrical signals over very long distances. Proteins are synthe￾sized, packaged, processed, stored, and released in different domains of the neuron. The synthesis of exportable proteins begins in the perikaryon. Preri￾bosomal subunits produced in the nucleolus enter the cytoplasm, where they are assembled and activated to form functional ribosomes. In some cases, they attach to membranous cisternae comprising the rough endo￾plasmic reticulum (Fig. 4). The outer nuclear mem￾brane ramifies within the cytoplasm as it encircles the nucleus and, studded with ribosomes, also becomes part of the protein synthetic apparatus. Messenger RNAs associated with ribosomes are translated into precursor proteins. The precursors are larger than the biologically active peptides and must be enzymatically cleaved and modified to attain their final form. Instructions about whether a given protein is destined for export are also encoded in the DNA of its precursor. A portion of the complemen￾tary messenger RNA is translated into a signal pep￾tide, which directs ribosomes to the cisternae of the rough endoplasmic reticulum. Peptides lacking a signal sequence cannot gain entry to the cisternae. The disposition and extent of rough endoplasmic Chapter 1 / Cytology and Organization of Cell Types 7