David Herman MacLennanOCOOntFRSFRSC (July 3, 1937 - June 24, 2020) was a Canadian biochemist and geneticist known for his basic work on proteins that regulate calcium flux through the sarcoplasmic reticulum (SR), thereby regulating muscle contraction and relaxation, and for his discoveries in the field of muscle diseases caused by genetic defects in calcium regulatory proteins.[1]
Born in Swan River, Manitoba, to Douglas MacLennan and Sigriður Sigurðardóttir, he received a BSA from the University of Manitoba in 1959 and a DSc (hc) in 2001.[2] He received MS (1961) and PhD (1963) degrees from Purdue University under Harry Beevers, and was then a postdoctoral fellow (1963–1964) under David E. Green and an assistant professor (1964–1968) at the University of Wisconsin–Madison. In 1969, he was appointed associate professor in the Banting and Best Department of Medical Research[3] and, later, professor (1974), chair (1978–1990), J. W. Billes Professor of Medical Research (1987–2007) and university professor (1993–2015).
MacLennan made fundamental contributions to our understanding of the mechanism of ion transport by SR calcium pumps, the storage of calcium in the SR by acidic lumenal proteins and the release of calcium from the SR by calcium release channels. He led teams that defined the genetic basis for the human skeletal muscle diseases, malignant hyperthermia, central core disease and Brody disease and was part of the team that demonstrated that mutations in phospholamban, a regulator of the calcium pump, can cause cardiomyopathy.[4] His identification of a calcium release channel mutation that causes porcine stress syndrome resulted in a diagnostic test that has decreased the incidence of the disease dramatically, with substantial economic benefits to the swine industry.
Honours and awards
1974 Ayerst Award of the Canadian Biochemical Society
A desmosome, also known as a macula adherens, is a cell structure specialized for cell-to-cell adhesion. A type of junctional complex, they are localized spot-like adhesions randomly arranged on the lateral sides of plasma membranes. Desmosomes are one of the stronger cell-to-cell adhesion types and are found in tissue that experience intense mechanical stress, such as cardiac muscle tissue, bladder tissue, gastrointestinal mucosa, and epithelia.
Hypertrophic cardiomyopathy is a condition in which muscle tissues of the heart become thickened without an obvious cause. The parts of the heart most commonly affected are the interventricular septum and the ventricles. This results in the heart being less able to pump blood effectively and also may cause electrical conduction problems.
SERCA, or sarcoplasmic/endoplasmic reticulum Ca2+-ATPase, or SR Ca2+-ATPase, is a calcium ATPase-type P-ATPase. Its major function is to transport calcium from the cytosol into the sarcoplasmic reticulum.
Phospholamban, also known as PLN or PLB, is a micropeptide protein that in humans is encoded by the PLN gene. Phospholamban is a 52-amino acid integral membrane protein that regulates the calcium (Ca2+) pump in cardiac muscle cells.
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited genetic disorder that predisposes those affected to potentially life-threatening abnormal heart rhythms or arrhythmias. The arrhythmias seen in CPVT typically occur during exercise or at times of emotional stress, and classically take the form of bidirectional ventricular tachycardia or ventricular fibrillation. Those affected may be asymptomatic, but they may also experience blackouts or even sudden cardiac death.
Troponin C is a protein which is part of the troponin complex. It contains four calcium-binding EF hands, although different isoforms may have fewer than four functional calcium-binding subdomains. It is a component of thin filaments, along with actin and tropomyosin. It contains an N lobe and a C lobe. The C lobe serves a structural purpose and binds to the N domain of troponin I (TnI). The C lobe can bind either Ca2+ or Mg2+. The N lobe, which binds only Ca2+, is the regulatory lobe and binds to the C domain of troponin I after calcium binding.
The Bowditch effect, also known as the Treppe phenomenon and the Treppe effect, is an autoregulation method by which myocardial tension increases with an increase in heart rate. It was first observed by Henry Pickering Bowditch in 1871.
Cardiac muscle troponin T (cTnT) is a protein that in humans is encoded by the TNNT2 gene. Cardiac TnT is the tropomyosin-binding subunit of the troponin complex, which is located on the thin filament of striated muscles and regulates muscle contraction in response to alterations in intracellular calcium ion concentration.
Ryanodine receptor 2 (RYR2) is one of a class of ryanodine receptors and a protein found primarily in cardiac muscle. In humans, it is encoded by the RYR2 gene. In the process of cardiac calcium-induced calcium release, RYR2 is the major mediator for sarcoplasmic release of stored calcium ions.
Troponin C, also known as TN-C or TnC, is a protein that resides in the troponin complex on actin thin filaments of striated muscle and is responsible for binding calcium to activate muscle contraction. Troponin C is encoded by the TNNC1 gene in humans for both cardiac and slow skeletal muscle.
Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 (SERCA1) also known as Calcium pump 1, is an enzyme that in humans is encoded by the ATP2A1 gene.
Telethonin, also known as Tcap, is a protein that in humans is encoded by the TCAP gene. Telethonin is expressed in cardiac and skeletal muscle at Z-discs and functions to regulate sarcomere assembly, T-tubule function and apoptosis. Telethonin has been implicated in several diseases, including limb-girdle muscular dystrophy, hypertrophic cardiomyopathy, dilated cardiomyopathy and idiopathic cardiomyopathy.
Myosin heavy chain, α isoform (MHC-α) is a protein that in humans is encoded by the MYH6 gene. This isoform is distinct from the ventricular/slow myosin heavy chain isoform, MYH7, referred to as MHC-β. MHC-α isoform is expressed predominantly in human cardiac atria, exhibiting only minor expression in human cardiac ventricles. It is the major protein comprising the cardiac muscle thick filament, and functions in cardiac muscle contraction. Mutations in MYH6 have been associated with late-onset hypertrophic cardiomyopathy, atrial septal defects and sick sinus syndrome.
Myosin essential light chain (ELC), ventricular/cardiac isoform is a protein that in humans is encoded by the MYL3 gene. This cardiac ventricular/slow skeletal ELC isoform is distinct from that expressed in fast skeletal muscle (MYL1) and cardiac atrial muscle (MYL4). Ventricular ELC is part of the myosin molecule and is important in modulating cardiac muscle contraction.
Cysteine and glycine-rich protein 3 also known as cardiac LIM protein (CLP) or muscle LIM protein (MLP) is a protein that in humans is encoded by the CSRP3 gene.
Sarcolipin is a micropeptide protein that in humans is encoded by the SLN gene.
Ryanodine receptor 1 (RYR-1) also known as skeletal muscle calcium release channel or skeletal muscle-type ryanodine receptor is one of a class of ryanodine receptors and a protein found primarily in skeletal muscle. In humans, it is encoded by the RYR1 gene.
Dario Renato Alessi is a French-born British biochemist, Director of the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit and Professor of Signal Transduction, at the School of Life Sciences, University of Dundee.
Bernard H. Bressler FCAHS is a Professor in the Department of Cellular and Physiological Sciences and an Associate Member in the Department of Orthopedics at the University of British Columbia (UBC).
Carol MacKintosh FRSB, is a cell and developmental biologist, Professor of Molecular Signalling and Head of Postgraduate Studies, at the School of Life Sciences, University of Dundee.
This page is based on this Wikipedia article Text is available under the CC BY-SA 4.0 license; additional terms may apply. Images, videos and audio are available under their respective licenses.
