r r r Cell Signalling Biology Michael J. Berridge Module 7 Cellular Processes 7 1 Module 7 Cellular Processes Synopsis Signalling pathways use different messenger systems acting through specific sensors and effectors to control a great variety of cell types (Module 7: Table cell inventory). Each specialized cell type has developed control mechanisms to suit their particular functions. For example, skeletal and cardiac muscle cells have very rapid signalling mechanisms capable of driving contraction within milliseconds. Smooth muscle cells tend to act more slowly, and are far more diverse in both their function and control mechanisms. Some cells contract in a conventional way in response to an external agonist, while others have more complex control mechanisms responsible for maintaining the tonic contraction of the smooth muscle cells surrounding blood vessels. Another example is cell secretion, where there is similar diversity in function and control. Preformed secretory products packaged into vesicles are released through a process of exocytosis. In exocrine glands and the intestine, there is a process of fluid secretion that depends upon the active transport of ions to provide the driving force for a parallel flow of water. Secretion is evident in many different cell types and cellular processes, such as transmitter release during presynaptic events in neurons, enzyme and fluid secretion by pancreatic acinar cells, release of insulin by insulin-secreting β-cells and inflammatory mediators by mast cells. Many of these mammalian cell types are controlled by more than one signalling pathway, and the object here is to understand how signalling pathways and their downstream sensors and effectors function to bring about a change in cellular activity in some typical examples of specialized cell types. Mammalian cell types Male germ cells There are a large number of mammalian cell types Neural stem cells (Module 7: Table cell inventory). They are adapted to per- form highly specific functions, which are controlled by Nervous system signalling systems uniquely adapted to carry out their par- Cortex ticular functions. These cell-specific signalsomes are a se- Dorsolateral prefrontal cortex (DLPFC) lection from the diverse array of intracellular signalling Cortical pyramidal neuron pathways (Module 2: Figure cell signalling pathways). Cortical inhibitory interneurons − During the process of cell differentiation, each primary Cajal Retzius neuron cell type expresses those signalling pathways that are par- Chandelier neurons ticularly suited to control their particular functions as il- Double bouquet neurons lustrated by some of the main mammalian cell types shown Martinotti interneurons below: Wide arbor (basket) interneurons Hippocampus Gametes Hippocampal CA1 neurons Oocytes Hippocampal CA3 neurons Spermatozoa Granule cells Stem cells Hippocampal interneurons Intestinal stem cells Axo-axonic cell Satellite cells + Basket cell (PV CCK-) Haematopoietic stem cells (HSCs) + Basket cell (PV- CCK ) Epidermal stem cells + + Basket cell (PV- CCK VIP ) Melanocyte stem cells Bis-stratified cell Mesenchymal stem cells Oriens-lacunosum molecular (O-LM) cell Mammary gland stem cells Schaffer-collateral-associated cell Green text indicates links to content within this module; blue text Lacunosum-moleculare-perforant path indicates links to content in other modules. (LM-PP) Please cite as Berridge, M.J. (2012) Cell Signalling Biology; Lacunosum-moleculare-radiatum- doi:10.1042/csb0001007 perforant path (LM-R-PP) C 2012 Portland Press Limited www.cellsignallingbiology.org Licensed copy. Copying is not permitted, except with prior permission and as allowed by law. r r r Cell Signalling Biology Michael J. Berridge Module 7 Cellular Processes 7 2 Trilaminar cell Microglia Back-projecting cell Pituicytes Hippocampal septal cell Oligodendrocytes Cerebellum Satellite glial cells Cerebellar Purkinje neurons Schwann cells Cerebellar climbing fibre Endothelium Basket cells Endothelial cells Neocortical neurons Skeletal muscle Starburst amacrine cells Slow-twitch muscle Thalamic interneurons Fast-twitch muscle IIa Suprachiasmatic nuclei (SCN) Fast-twitch muscle IId/x Medium spiny neurons Fast-twitch muscle IIba D1 dopamine receptor-expressing MSNs (D1 + Satellite cells MSNs) Cardiac cells D2 dopamine receptor-expressing MSNs (D2 + Sinoatrial node pacemaker cells MSNs) Purkinje fibres Hypothalamus Atrial cells Magnocellular (MCN) neurons Ventricular cells Oxytocin neurons Smooth muscle Vasopressin neurons Smooth muscle pacemaker cells Anterior pituitary Interstitial cells of Cajal Corticotrophs Atypical smooth muscle cells Gonadotrophs Smooth muscle cells Lactotrophs Airway smooth muscle cells Somatotrophs Corpus cavernosum smooth muscle cell Thyrotrophs Detrusor smooth muscle cell Folliculostellate (FS) cells Gastrointestinal smooth muscle cells Sensory systems Ureter smooth muscle cells Hearing Urethral smooth muscle cells Outer hair cells Uterine smooth muscle cells Inner hair cells Vascular smooth muscle cells Hypoxia-sensing Vas deferens Glomus cells (see carotid body Module 10: Figure Parathyroid gland carotid body chemoreception) Chief cells Sustentacular cell Thyroid gland Neuroepithelial bodies Thyroid follicular cells Nociception C cells Aα sensory fibres Bone/cartilage Aβ sensory fibres Osteoblasts Aδ sensory fibres Osteoclasts Cfibres Osteocytes Olfaction Chondrocytes Olfactory receptor cells Skin Osmoreception Arrector pilli muscle Organum vasculosum of the lamina terminalis Keratinocytes (OVLT) neuron Melanocytes Subfornical organ (SFO) neuron Sebaceous gland Photoreception Sweat gland secretory coil cells Cones Sweat gland reabsorptive duct cells Rods Alimentary canal Taste Stomach Type I glial-like cells Parietal cells Type II receptor cells D cells Type III presynaptic cells G cells Touch Enterochromaffin-like cell (ECL cell) Merkel cells X/A-like cells Glial cells Intestine Astrocytes Small intestine Bergmann glia Enterochromaffin cell Muller¨ cells L cell C 2012 Portland Press Limited www.cellsignallingbiology.org r r r Cell Signalling Biology Michael J. Berridge Module 7 Cellular Processes 7 3 Colon systems that act on the feeding and satiety centres in Kidney the brain (Module 7: Figure control of food intake). Kidney tubule cells • Sites of inflammation and wounding draw together Proximal convoluted tubule (PCT) many of the cells such as macrophages, neutrophils, Loop of Henle mast cells and endothelial cells that co-operate with each Distal convoluted tubule (DCT) other to fight off infections and to restore tissue integ- Collecting duct cells rity (Module 11: Figure inflammation). Juxtaglomerular apparatus • A number of cell types contribute to Ca2 + homoeostasis Extraglomerular mesangial cells (lacis cells) (Module 7: Figure Ca2 + homoeostasis). Intraglomerular mesangial cells • Blood pressure is regulated by a complex cellular and Macula densa cells hormonal network responsible for blood Na + regula- Renin-producing glomerular cells tion (Module 7: blood pressure control). Salivary gland • Bone remodelling depends upon an interaction between Pancreas the different bone cells (Module 7: Figure bone cells). Islets of Langerhans Glucagon-secreting α-cells Insulin-secreting β-cells Metabolic energy network Exocrine pancreas The primary function of the metabolic energy network is Exocine pancreatic acinar cells to manage the energy status of the cell (Module 7: Fig- Exocrine pancreatic centroacinar cells ure metabolic energy network). Energy is derived from Liver the intake of food, which is processed in the intestine to Liver cells form the high-energy metabolites such as amino acids, free Kupffer cells fatty acids and glucose that then circulate in the plasma to Hepatic stellate cells be dealt with by cells that participate in the metabolic net- Adrenal gland work. In addition, there are other cells that monitor various Adrenal cortex parameters of the energy supply and then release appro- Zona glomerulosa cells priate hormonal signals to make adjustments to different Zona fasciculata/reticularis cells components of the network. The energy supply is dealt Adrenal medulla with in two ways: most of the energy is consumed by a Chromaffin cells variety of cellular processes, while any excess is then stored Adipose tissue either as triacylglycerols in the white fat cells or as glycogen White fat cells in the liver cells. Metabolic homoeostasis depends on en- Brown fat cells ergy consumption closely matching energy supply. If con- Haematopoietic cells sumption exceeds supply, then energy is mobilized from Blood platelets the energy stores to maintain equilibrium. Since the energy B cells stores are finite, such an imbalance in energy supply begins T cells to cause severe wasting as the process of autophagy kicks in Neutrophils to begin to mobilize energy from the structural compon- Macrophages ents of cells. Conversely, if the supply of energy exceeds Tingible body macrophages energy consumption, the excess is diverted into the energy Mast cells stores, resulting in obesity. This balance between energy uptake and expenditure is determined by the control of In many cases, different cell types are collected together food intake and body weight. into complex functional networks: The numbers on Module 7: Figure metabolic energy network refer to some of the major components of the • Neural circuits in the brain are built up from interactions network that determines energy homoeostasis: between different neurons, as occurs in the cerebellum (Module 10: Figure