Chapter 1/Cytology and Organization of Cell Types 9 The vesicle membrane contains proteins that regulate cisternae of the rough endoplasmic reticulum. One of the internal vesicular environment. On the appropriate the most morphologically complex variations of these signal, active neuropeptides are released by exocytosis, structures resides in the dendritic spine, where paral which is fusion of the vesicle membrane with the plasma lel, smooth-surfaced cisternae alternate with electron- membrane at the presynaptic site. dense bands of unknown composition All of the diverse structures are thought to func- 2.2. 2. PROTEINS SYNTHESIZED FOR USE WITHIN tion in the release and sequestration of calcium THE NEURON within the neuron Calcium is central to most aspects The synthesis of exportable proteins represents of neuronal function, including membrane perme- only a portion of the total protein synthetic effort ability; mediation of the effects of neurotransmit- by the neuron. The elaboration of the cytoskeletal ters, hormones, and growth factors; cytoskeletal framework and the synthesis of other proteins includ- function; and vesicle release. In neurons,calcium mobilization is achieved, at least in part, by the tems, and other proteins destined for maintenance binding of inositol 1, 4, 5-triphosphate (IP)to intra and renewal of the cytoplasm and its organelles also cellular receptors located on the aforementioned depend on translation of messenger RNAS. These membranous cisternae. IP is a second messenger proteins are synthesized on free ribosomes that are generated on receptor-stimulated hydrolysis of plentiful in all nerve cells. Axons possess a highly phosphatidylinositol 4, 5-biphosphate by phospholi- organized transport system to convey proteins to pase C, an enzyme activated by signal transduction presynaptic terminals or back to the cell body. mechanisms Dendrites, their postsynaptic specializations, and dendritic spines also require proteins for growth, 2. 4. Mitochondria maintenance, and function. Although there is an 2.. MITOCHONDRIAL STRUCTURE IN NEURONS indication of molecular transport to these sites, the identities of the molecules and the nature of the Mitochondria from various brain regions and transport mechanism has just begun to be explored. neuronal, compartments(perikarya, dendrites, Moreover, evidence for local protein synthesis sug- brane architecture. Mitochondria in neurons con- gests that not all dendritic and postsynaptic proteins tain interconnected tubular and lamellar cristae, arrive from the cell body. The presence of polyribo tions and at the base of dendritic spines provides ipherally and the lamellar ones located more cen the machinery for local protein synthesis. The exis- tence of local protein synthetic mechanisms is further is unknown, although changes in cristae shape may supported by the presence of some messenger RNAs contribute to regulation of ATP production. The in distant dendritic arbors, suggesting that growth- outer mitochondrial membranes are also in close dependent and activity-dependent synaptic alterations association with membranes of the endoplasmic reti including changes in morphology, may be regulated culum, at sites of high calcium generation. Some partially by the local synthesis of key synaptic proteins. dria in the soma, the axon hillock, the nodes of Ranvier, and the nerve terminal; during neuronal development, mitochondria are also located in 2.3. Smooth Membrane Compartments in growth cones Neurons Serve as Reservoirs for Calcium In addition to the intramembranous compartments 2.4.2. MITOCHONDRIAL FUNCTION IN NEURONS that directly participate in the synthesis, packaging, Mitochondria are present in all cells and provide and transport of secretory peptides, other cisternal common functions irrespective of the particular cell and vesicular structures are evident within the various type. These functions include the generation of ATP domains of the neuron. The membranous sacs are as well as reactive oxygen species, intermediary visible as smooth-surfaced compartments in a variety metabolism, intracellular calcium signaling, and of configurations. Some appear as relatively short the regulation of apoptosis. However, the unique sacs, but others are longer and anastomose within compartmentalization of neurons into different neuronal processes. In the cell body, smooth mem- structural and functional domains and their high brane profiles are arranged in stacks or emanate from energy requirements necessitate an expanded roleThe vesicle membrane contains proteins that regulate the internal vesicular environment. On the appropriate signal, active neuropeptides are released by exocytosis, which is fusion of the vesicle membrane with the plasma membrane at the presynaptic site. 2.2.2. PROTEINS SYNTHESIZED FOR USE WITHIN THE NEURON The synthesis of exportable proteins represents only a portion of the total protein synthetic effort by the neuron. The elaboration of the cytoskeletal framework and the synthesis of other proteins includ￾ing ion channels, receptors, second messenger sys￾tems, and other proteins destined for maintenance and renewal of the cytoplasm and its organelles also depend on translation of messenger RNAs. These proteins are synthesized on free ribosomes that are plentiful in all nerve cells. Axons possess a highly organized transport system to convey proteins to presynaptic terminals or back to the cell body. Dendrites, their postsynaptic specializations, and dendritic spines also require proteins for growth, maintenance, and function. Although there is an indication of molecular transport to these sites, the identities of the molecules and the nature of the transport mechanism has just begun to be explored. Moreover, evidence for local protein synthesis sug￾gests that not all dendritic and postsynaptic proteins arrive from the cell body. The presence of polyribo￾somes beneath postsynaptic membrane specializa￾tions and at the base of dendritic spines provides the machinery for local protein synthesis. The exis￾tence of local protein synthetic mechanisms is further supported by the presence of some messenger RNAs in distant dendritic arbors, suggesting that growth￾dependent and activity-dependent synaptic alterations, including changes in morphology, may be regulated partially by the local synthesis of key synaptic proteins. 2.3. Smooth Membrane Compartments in Neurons Serve as Reservoirs for Calcium In addition to the intramembranous compartments that directly participate in the synthesis, packaging, and transport of secretory peptides, other cisternal and vesicular structures are evident within the various domains of the neuron. The membranous sacs are visible as smooth-surfaced compartments in a variety of configurations. Some appear as relatively short sacs, but others are longer and anastomose within neuronal processes. In the cell body, smooth mem￾brane profiles are arranged in stacks or emanate from cisternae of the rough endoplasmic reticulum. One of the most morphologically complex variations of these structures resides in the dendritic spine, where paral￾lel, smooth-surfaced cisternae alternate with electron￾dense bands of unknown composition. All of the diverse structures are thought to func￾tion in the release and sequestration of calcium within the neuron. Calcium is central to most aspects of neuronal function, including membrane perme￾ability; mediation of the effects of neurotransmit￾ters, hormones, and growth factors; cytoskeletal function; and vesicle release. In neurons, calcium mobilization is achieved, at least in part, by the binding of inositol 1,4,5-triphosphate (IP) to intra￾cellular receptors located on the aforementioned membranous cisternae. IP is a second messenger generated on receptor-stimulated hydrolysis of phosphatidylinositol 4,5-biphosphate by phospholi￾pase C, an enzyme activated by signal transduction mechanisms. 2.4. Mitochondria 2.4.1. MITOCHONDRIAL STRUCTURE IN NEURONS Mitochondria from various brain regions and neuronal compartments (perikarya, dendrites, axons, and synapses) have essentially uniform mem￾brane architecture. Mitochondria in neurons con￾tain interconnected tubular and lamellar cristae, with the tubular-shaped cristae arranged more per￾ipherally and the lamellar ones located more cen￾trally. The functional significance of these features is unknown, although changes in cristae shape may contribute to regulation of ATP production. The outer mitochondrial membranes are also in close association with membranes of the endoplasmic reti￾culum, at sites of high calcium generation. Some neurons display a higher accumulation of mitochon￾dria in the soma, the axon hillock, the nodes of Ranvier, and the nerve terminal; during neuronal development, mitochondria are also located in growth cones. 2.4.2. MITOCHONDRIAL FUNCTION IN NEURONS Mitochondria are present in all cells and provide common functions irrespective of the particular cell type. These functions include the generation of ATP, as well as reactive oxygen species, intermediary metabolism, intracellular calcium signaling, and the regulation of apoptosis. However, the unique compartmentalization of neurons into different structural and functional domains and their high￾energy requirements necessitate an expanded role Chapter 1 / Cytology and Organization of Cell Types 9