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Introduction: The chromaffin cell
seminars in
CELL & DEVELOPMENTAL BIOLOGY, Vol 8, 1997: pp 99–100
Introduction: The chromaffin cell Robert D. Burgoyne
transmission and perhaps secretion from other cell types. Stimulation of adrenal chromaffin cells leads not only to secretion of catecholamines and stored peptides but to the activation of mechanisms for increased synthesis of secretory components. One particular example of this is the increased activity and expression of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis. The signalling mechanisms that control expression of tyrosine hydroxylase through gene transcription are described in the first review by Sabban. A considerable amount of work on the control of chromaffin cell function has been based on the use of primary cell cultures or the use of the tumor cell counterpart, the PC12 cell line derived from a rat adrenal medullary phaeochromocytoma. More recently, attention has been directed again at the physiological regulation of catecholamine secretion and this can be studied most readily in the rat. The various approaches to the study of the control of secretion from rat adrenal gland are described in the review by Borges. The ability to purify the chromaffin cell secretory granule, the chromaffin granule, in reasonable purity and in high quantities has led to these organelles being characterized in detail. With the exception of the synaptic vesicle, the chromaffin granule is probably the most characterized secretory vesicle and Apps has reviewed what is now known about the content proteins of the chromaffin granules as well as the membrane proteins involved in granule bioenergetics, membrane transport and exocytosis. The major intracellular signal leading to secretion from chromaffin cells is an elevation in cytosolic free Ca2 + concentration. The most important mechanism for direct activation of exocytosis is external Ca2 + entry across the plasma membrane but chromaffin cells possess intracellular Ca2 + stores sensitive to IP3 or to ryanodine that have important roles in Ca2 + homeostasis and have now been well characterized from imaging and quantitative single cell measurements. The kinetics of Ca2 + -regulated exocytosis have been studied using permeabilized cells but most effectively by the use of high-resolution patch-clamp techniques. The chromaffin cells were actually the
ESSENTIALLY ALL CELL TYPES possess a constitutive secretory pathway. In addition, certain specialized secretory cells also possess a very prominent regulated secretory pathway that allows the accumulation of a wide variety of extracellularly-acting molecules and their release only following cell activation. Specialized regulated secretory cells include neurons, neuroendocrine and endocrine cells, exocrine cells, sperm, lung epithelial cells and many others. Very recently, it has become increasingly apparent that other cell types including even fibroblastic cells, for example, do possess the ability to store and secrete in response to an intracellular Ca2 + signal indicating a potential universal cellular distribution of the regulated secretory mechanism. Adrenal chromaffin cells, the subject of this collection of reviews, secrete the catecholamines adrenaline and noradrenaline (from two different cell types) as well as a range of proteins and peptides which are all stored in the same large dense-core secretory granules. During embryogenesis these cells are derived from the same precursors as sympathetic neurons and so, while they have the morphological appearance of endocrine cells, they possess many features in common with neurons. Historically, work on adrenal chromaffin cells has been crucial for important advances in the study of exocytosis/neurotransmission. The first demonstration of acetylcholine as a transmitter by Feldberg and co-workers in 1934 was based on analysis of the control of adrenaline release from adrenal chromaffin cells. In addition, the concept of the involvement of intracellular Ca2 + in stimulus secretion coupling came from the work of Bill Douglas on chromaffin cells. For many years now, the adrenal chromaffin cell has been intensively studied as a model for the investigation of the regulated secretory pathway. It has been believed that these cells would allow the generation of insights applicable, at least, to hormone synthesis and release from endocrine cells but also to synaptic neuro-
From The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK ©1997 Academic Press Ltd/sr960128
99
Introduction first cell type to be used in the development by Marty and Neher of capacitance measurement for direct analysis of changes in plasma membrane area during exocytosis/endocytosis. The information on exocytosis kinetics has allowed the development of multi-step models of the exocytotic pathway (reviewed by Gillis and Chow) which provide an important base-line for future understanding of the mechanisms of action of particular proteins that are involved in Ca2 + -regulated exocytosis. Following the original notion that the chromaffin cell could act as a model for neuronal (particularly dense-core granule) as well as endocrine exocytosis, differences in the detailed kinetics and control of
exocytosis began to cast doubts on this idea. Over the last couple of years, however, we have seen a revolution in our understanding of the proteins involved in exocytosis. Much of the new information has come from the identification of synaptic proteins in neurotransmission. It is now quite clear that the proteins that function in neurotransmission do also act in adrenaline release from chromaffin cells (reviewed by Morgan and Burgoyne) and indeed may be universal components of the Ca2 + -regulated exocytotic machinery. The chromaffin cell has, therefore, been reaffirmed as a key model for the study of the cell biology of the regulated secretory pathway.
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CELL & DEVELOPMENTAL BIOLOGY, Vol 8, 1997: pp 99–100
Introduction: The chromaffin cell Robert D. Burgoyne
transmission and perhaps secretion from other cell types. Stimulation of adrenal chromaffin cells leads not only to secretion of catecholamines and stored peptides but to the activation of mechanisms for increased synthesis of secretory components. One particular example of this is the increased activity and expression of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis. The signalling mechanisms that control expression of tyrosine hydroxylase through gene transcription are described in the first review by Sabban. A considerable amount of work on the control of chromaffin cell function has been based on the use of primary cell cultures or the use of the tumor cell counterpart, the PC12 cell line derived from a rat adrenal medullary phaeochromocytoma. More recently, attention has been directed again at the physiological regulation of catecholamine secretion and this can be studied most readily in the rat. The various approaches to the study of the control of secretion from rat adrenal gland are described in the review by Borges. The ability to purify the chromaffin cell secretory granule, the chromaffin granule, in reasonable purity and in high quantities has led to these organelles being characterized in detail. With the exception of the synaptic vesicle, the chromaffin granule is probably the most characterized secretory vesicle and Apps has reviewed what is now known about the content proteins of the chromaffin granules as well as the membrane proteins involved in granule bioenergetics, membrane transport and exocytosis. The major intracellular signal leading to secretion from chromaffin cells is an elevation in cytosolic free Ca2 + concentration. The most important mechanism for direct activation of exocytosis is external Ca2 + entry across the plasma membrane but chromaffin cells possess intracellular Ca2 + stores sensitive to IP3 or to ryanodine that have important roles in Ca2 + homeostasis and have now been well characterized from imaging and quantitative single cell measurements. The kinetics of Ca2 + -regulated exocytosis have been studied using permeabilized cells but most effectively by the use of high-resolution patch-clamp techniques. The chromaffin cells were actually the
ESSENTIALLY ALL CELL TYPES possess a constitutive secretory pathway. In addition, certain specialized secretory cells also possess a very prominent regulated secretory pathway that allows the accumulation of a wide variety of extracellularly-acting molecules and their release only following cell activation. Specialized regulated secretory cells include neurons, neuroendocrine and endocrine cells, exocrine cells, sperm, lung epithelial cells and many others. Very recently, it has become increasingly apparent that other cell types including even fibroblastic cells, for example, do possess the ability to store and secrete in response to an intracellular Ca2 + signal indicating a potential universal cellular distribution of the regulated secretory mechanism. Adrenal chromaffin cells, the subject of this collection of reviews, secrete the catecholamines adrenaline and noradrenaline (from two different cell types) as well as a range of proteins and peptides which are all stored in the same large dense-core secretory granules. During embryogenesis these cells are derived from the same precursors as sympathetic neurons and so, while they have the morphological appearance of endocrine cells, they possess many features in common with neurons. Historically, work on adrenal chromaffin cells has been crucial for important advances in the study of exocytosis/neurotransmission. The first demonstration of acetylcholine as a transmitter by Feldberg and co-workers in 1934 was based on analysis of the control of adrenaline release from adrenal chromaffin cells. In addition, the concept of the involvement of intracellular Ca2 + in stimulus secretion coupling came from the work of Bill Douglas on chromaffin cells. For many years now, the adrenal chromaffin cell has been intensively studied as a model for the investigation of the regulated secretory pathway. It has been believed that these cells would allow the generation of insights applicable, at least, to hormone synthesis and release from endocrine cells but also to synaptic neuro-
From The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool, L69 3BX, UK ©1997 Academic Press Ltd/sr960128
99
Introduction first cell type to be used in the development by Marty and Neher of capacitance measurement for direct analysis of changes in plasma membrane area during exocytosis/endocytosis. The information on exocytosis kinetics has allowed the development of multi-step models of the exocytotic pathway (reviewed by Gillis and Chow) which provide an important base-line for future understanding of the mechanisms of action of particular proteins that are involved in Ca2 + -regulated exocytosis. Following the original notion that the chromaffin cell could act as a model for neuronal (particularly dense-core granule) as well as endocrine exocytosis, differences in the detailed kinetics and control of
exocytosis began to cast doubts on this idea. Over the last couple of years, however, we have seen a revolution in our understanding of the proteins involved in exocytosis. Much of the new information has come from the identification of synaptic proteins in neurotransmission. It is now quite clear that the proteins that function in neurotransmission do also act in adrenaline release from chromaffin cells (reviewed by Morgan and Burgoyne) and indeed may be universal components of the Ca2 + -regulated exocytotic machinery. The chromaffin cell has, therefore, been reaffirmed as a key model for the study of the cell biology of the regulated secretory pathway.
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