Sir Michael Berridge | |
---|---|
Born | Michael John Berridge [1] 22 October 1938 |
Died | 13 February 2020 81) [1] | (aged
Education | University College of Rhodesia and Nyasaland (Bsc) University College (PhD) |
Known for | Cell signaling research Discovery of inositol trisphosphate as second messenger |
Awards | King Faisal International Prize in Science Louis-Jeantet Prize for Medicine Knight Bachelor Canada Gairdner International Award Albert Lasker Award for Basic Medical Research Royal Medal Dr H. P. Heineken Prize for Biochemistry and Biophysics Shaw Prize in Life Science and Medicine |
Scientific career | |
Fields | Physiology Biochemistry |
Institutions | University of Virginia Case Western Reserve University University of Cambridge Babraham Institute |
Thesis | The physiology of excretion in the cotton stainer, Dysdercus fasciatus Signoret (Hemiptera, Pyrrhocoridae) (1964) |
Doctoral advisor | Vincent Wigglesworth |
Notable students | Antony Galione [3] |
Sir Michael John "Mike" Berridge FRS FMedSci FBPhS [4] (22 October 1938 - 13 February 2020) was a British physiologist and biochemist. He was known for his work on cell signaling, in particular the discovery that inositol trisphosphate acts as a second messenger, linking events at the plasma membrane with the release of calcium ions (Ca2+) within the cell.
Berridge was born in Gatooma (now Kadoma, Zimbabwe) in Southern Rhodesia (now Zimbabwe). His high school biology teacher convinced him and his parents that he should pursue tertiary education, and he entered the newly founded University of Rhodesia and Nyasaland (now University of Zimbabwe), [5] earning his Bsc in zoology and chemistry in 1960. [6]
He became interested in insect physiology after helping with his physiology professor's research on tsetse flies, and went to the United Kingdom to study with Vincent Wigglesworth, regarded as the father of insect physiology, at the Department of Zoology of the University of Cambridge. Berridge became a member at the Gonville and Caius College, where Wigglesworth was a fellow, [5] and obtained his PhD in 1965. [7]
Initially intending to return to Southern Rhodesia (now Zimbabwe) after his PhD, Berridge's plan was thwarted by the Rhodesian Bush War. He migrated to the United States instead, joining the Department of Biology of the University of Virginia as a postdoctoral fellow. [5] A year later, he moved to the Developmental Biology Center of Case Western Reserve University. He became a research associate under Bodil Schmidt-Nielsen at the Department of Biology of the same university in 1967. [7]
In 1969, John Treherne invited Berridge to return to the University of Cambridge and join the new Unit of Invertebrate Chemistry and Physiology that he was setting up in the Department of Zoology. [5] He first joined as a senior scientific officer, and was promoted to principal scientific officer in 1972. He became a senior principal scientific officer at the Unit of Insect Neurophysiology and Pharmacology, also at the University of Cambridge, in 1978. [7]
In 1990, Berridge joined the Babraham Institute as the Deputy Chief Scientific Officer of the Laboratory of Molecular Signalling, before serving as the Head of Signalling in 1996 until retiring in 2003. [8] After retirement, Berridge was appointed as Babraham's first emeritus Babraham Fellow. [9]
Berridge was a fellow of the Trinity College of the University of Cambridge from 1972 until his death. [6]
Berridge maintained an online textbook on cell signalling, now hosted by Portland Press under the Biochemical Society. [10]
Berridge had been studying cell signaling when he was at Case Western Reserve University, where he received advice from Theodore W. Rall, co-discoverer of the second messenger cyclic AMP with Earl Wilbur Sutherland Jr., who had also worked at Case Western Reserve. [11] Working on the salivary glands of a blow fly species, Berridge showed cyclic AMP produced the same physiological effect as serotonin, dramatically increasing saliva secretion. [12] The idea of second messenger was new at the time, and his finding supported cyclic AMP as a second messenger of serotonin.
He continued studying cyclic AMP after returning to the University of Cambridge, and conducted experiments to study how serotonin and cyclic AMP affected the movement of ions, as ion concentration difference across the salivary gland epithelium controlled the movement of water across the epithelium through osmosis. Berridge measured the difference in electric potential across the epithelium since ions are charged. [11]
Surprisingly, he found that serotonin and cyclic AMP produced opposite effect to ion movement. While the former reduced the transepithelial potential difference closer to zero, the latter caused an even more negative difference. This suggested cyclic AMP caused positively-charged ions to move across the epithelium from the extracellular fluid to the inside of the salivary gland (known as the lumen). [13]
Berridge suspected calcium ions (Ca2+) could explain the distinct electrical but similar physiological effects of serotonin and cyclic AMP. In 1971, Howard Rasmussen, one of the first researchers to recognise the role of Ca2+ as a second messenger, was on a sabbatical at Cambridge. [5] He and Rasmussen worked together and found serotonin triggered the release of Ca2+ from a storage inside the cell. [14] Later, he confirmed that serotonin activated two distinct receptor system, one through cyclic AMP and the other through Ca2+. [15]
Berridge then wanted to identify the connection between cell surface receptor activation and the release of intracellular Ca2+ from storage. He was inspired by a review article by Robert H. Michell in 1975, which proposed receptor activation caused the breakdown of phosphatidylinositol, which in turn opened Ca2+ channels on the cell membrane to allowing Ca2+ influx into cells. [16] He hypothesised phosphatidylinositol was hydrolysed into a form of inositol phosphate and diglyceride (DAG), and the former was eventually broken down into inositol. He applied lithium ions to blow fly salivary glands to inhibit the conversion of inositol phosphate to inositol.
With help from Rex Malcolm Chaplin Dawson, who was studying inositol at the Babraham Institute near Cambridge, Berridge found that phosphatidylinositol was hydrolysed into IP3 and DAG. [17] Later the same year, he confirmed IP3 released Ca2+ from the intracellular storage, which he identified as the endoplasmic reticulum. [18] This report, together with Yasutomi Nishizuka's discovery that DAG was a second messenger in its own right and could activate protein kinase C, [19] marked the start of the field of calcium signaling. [20]
The Sir Michael Berridge Prize at the Babraham Institute was named in his honour and established with his endowment. [41]
Adenylate cyclase is an enzyme with systematic name ATP diphosphate-lyase . It catalyzes the following reaction:
Cyclic adenosine monophosphate is a second messenger, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transduction in many different organisms, conveying the cAMP-dependent pathway.
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. They are coupled with G proteins. They pass through the cell membrane seven times in the form of six loops of amino acid residues, which is why they are sometimes referred to as seven-transmembrane receptors. Ligands can bind either to the extracellular N-terminus and loops or to the binding site within transmembrane helices. They are all activated by agonists, although a spontaneous auto-activation of an empty receptor has also been observed.
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell to its interior. Their activity is regulated by factors that control their ability to bind to and hydrolyze guanosine triphosphate (GTP) to guanosine diphosphate (GDP). When they are bound to GTP, they are 'on', and, when they are bound to GDP, they are 'off'. G proteins belong to the larger group of enzymes called GTPases.
Inositol trisphosphate or inositol 1,4,5-trisphosphate abbreviated InsP3 or Ins3P or IP3 is an inositol phosphate signaling molecule. It is made by hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2), a phospholipid that is located in the plasma membrane, by phospholipase C (PLC). Together with diacylglycerol (DAG), IP3 is a second messenger molecule used in signal transduction in biological cells. While DAG stays inside the membrane, IP3 is soluble and diffuses through the cell, where it binds to its receptor, which is a calcium channel located in the endoplasmic reticulum. When IP3 binds its receptor, calcium is released into the cytosol, thereby activating various calcium regulated intracellular signals.
The sodium–potassium pump is an enzyme found in the membrane of all animal cells. It performs several functions in cell physiology.
Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of all muscle cell types, and in fertilization. Many enzymes require calcium ions as a cofactor, including several of the coagulation factors. Extracellular calcium is also important for maintaining the potential difference across excitable cell membranes, as well as proper bone formation.
Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-receptor stimulated by acetylcholine released from postganglionic fibers in the parasympathetic nervous system.
CREB-TF is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first described in 1987 as a cAMP-responsive transcription factor regulating the somatostatin gene.
Cyclic nucleotide–gated ion channels or CNG channels are ion channels that function in response to the binding of cyclic nucleotides. CNG channels are nonselective cation channels that are found in the membranes of various tissue and cell types, and are significant in sensory transduction as well as cellular development. Their function can be the result of a combination of the binding of cyclic nucleotides and either a depolarization or a hyperpolarization event. Initially discovered in the cells that make up the retina of the eye, CNG channels have been found in many different cell types across both the animal and the plant kingdoms. CNG channels have a very complex structure with various subunits and domains that play a critical role in their function. CNG channels are significant in the function of various sensory pathways including vision and olfaction, as well as in other key cellular functions such as hormone release and chemotaxis. CNG channels have also been found to exist in prokaryotes, including many spirochaeta, though their precise role in bacterial physiology remains unknown.
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. Second messengers trigger physiological changes at cellular level such as proliferation, differentiation, migration, survival, apoptosis and depolarization.
The Babraham Institute is a life sciences research institution focussing on healthy ageing. The Babraham Institute is based on the Babraham Research Campus, partly occupying a former manor house, but also laboratory and science facility buildings on the campus, surrounded by an extensive parkland estate, just south of Cambridge, England. It is an independent and charitable organization which is involved in biomedical research, including healthy aging and molecular biology. The director is Dr Simon Cook who also leads the Institute's signalling research programme.
Calcium signaling is the use of calcium ions (Ca2+) to communicate and drive intracellular processes often as a step in signal transduction. Ca2+ is important for cellular signalling, for once it enters the cytosol of the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins. Ca2+ can act in signal transduction resulting from activation of ion channels or as a second messenger caused by indirect signal transduction pathways such as G protein-coupled receptors.
In the nervous system, a synapse is a structure that permits a neuron to pass an electrical or chemical signal to another neuron or to the target effector cell.
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a Ca2+-mobilizing second messenger synthesised in response to extracellular stimuli. Like its mechanistic cousins, IP3 and cyclic adenosine diphosphoribose (Cyclic ADP-ribose), NAADP binds to and opens Ca2+ channels on intracellular organelles, thereby increasing the intracellular Ca2+ concentration which, in turn, modulates sundry cellular processes (see Calcium signalling). Structurally, it is a dinucleotide that only differs from the house-keeping enzyme cofactor, NADP by a hydroxyl group (replacing the nicotinamide amino group) and yet this minor modification converts it into the most potent Ca2+-mobilizing second messenger yet described. NAADP acts across phyla from plants to humans.
2-Aminoethoxydiphenyl borate (2-APB) is a chemical that acts to inhibit both IP3 receptors and TRP channels (although it activates TRPV1, TRPV2, & TRPV3 at higher concentrations). In research it is used to manipulate intracellular release of calcium ions (Ca2+) and modify TRP channel activity, although the lack of specific effects make it less than ideal under some circumstances. Additionally, there is evidence that 2-APB acts directly to inhibit gap junctions made of connexin. Increasing evidence showed that 2-APB is a powerful modifier of store-operated calcium channels (SOC) function, low concentration of 2-APB can enhance SOC while high concentration induces a transient increase followed by complete inhibition.
Phospholipase C (PLC) is a class of membrane-associated enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which play an important role in eukaryotic cell physiology, in particular signal transduction pathways. Phospholipase C's role in signal transduction is its cleavage of phosphatidylinositol 4,5-bisphosphate (PIP2) into diacyl glycerol (DAG) and inositol 1,4,5-trisphosphate (IP3), which serve as second messengers. Activators of each PLC vary, but typically include heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca2+, and phospholipids.
In the field of molecular biology, the cAMP-dependent pathway, also known as the adenylyl cyclase pathway, is a G protein-coupled receptor-triggered signaling cascade used in cell communication.
Calcium encoding (also referred to as Ca2+ encoding or calcium information processing) is an intracellular signaling pathway used by many cells to transfer, process and encode external information detected by the cell. In cell physiology, external information is often converted into intracellular calcium dynamics. The concept of calcium encoding explains how Ca2+ ions act as intracellular messengers, relaying information within cells to regulate their activity. Given the ubiquity of Ca2+ ions in cell physiology, Ca2+ encoding has also been suggested as a potential tool to characterize cell physiology in health and disease. The mathematical bases of Ca2+ encoding have been pioneered by work of Joel Keizer and Hans G. Othmer on calcium modeling in the 1990s and more recently they have been revisited by Eshel Ben-Jacob, Herbert Levine and co-workers.
Antony Giuseppe Galione is a British pharmacologist. He is a professor and Wellcome Trust senior investigator in the Department of Pharmacology at the University of Oxford.