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550 results on '"Trybus, Kathleen M."'

109. Addition of lysines to the 50/20 kDa junction of myosin strengthens weak binding to actin without affecting the maximum ATPase activity

Author

Joel, Peteranne B., Sweeney, H. Lee, and Trybus, Kathleen M.

Subjects
Adenosine diphosphate -- Physiological aspects, Actin -- Physiological aspects, Lysine -- Physiological aspects, Myosin -- Physiological aspects, Biochemistry -- Research, Biological sciences, Chemistry
Abstract

Research has been conducted on smooth muscle heavy meromyosin. The authors have investigated the effects of increasing positive charge in loop 2 variable portion of the meromyosin, and the results demonstrate that loop 2 is responsible for setting the affinity for actin, and for the release and motility of adenosine diphosphate.

Published
2003

110. Unusual dynamics of the divergent malaria parasite PfAct1 actin filament.

Author

Hailong Lu, Fagnant, Patricia M., and Trybus, Kathleen M.

Subjects
PLASMODIUM, FIBERS, CELL motility, FLUORESCENCE microscopy
Abstract

Gliding motility and host cell invasion by the apicomplexan parasite Plasmodium falciparum (Pf), the causative agent of malaria, is powered by a macromolecular complex called the glideosome that lies between the parasite plasma membrane and the inner membrane complex. The glideosome core consists of a singleheaded class XIV myosin PfMyoA and a divergent actin PfAct1. Here we use total internal reflection fluorescence microscopy to visualize growth of individual unstabilized PfAct1 filaments as a function of time, an approach not previously used with this actin isoform. Although PfAct1 was thought to be incapable of forming long filaments, filaments grew as long as 30 µm. Polymerization occurs via a nucleation-elongation mechanism, but with an ~4 µM critical concentration, an order-of-magnitude higher than for skeletal actin. Protomers disassembled from both the barbed and pointed ends of the actin filament with similar fast kinetics of 10 to 15 subunits/s. Rapid treadmilling, where the barbed end of the filament grows and the pointed end shrinks while maintaining an approximately constant filament length, was visualized near the critical concentration. Once ATP has been hydrolyzed to ADP, the filament becomes very unstable, resulting in total dissolution in <40 min. Dynamics at the filament ends are suppressed in the presence of inorganic phosphate or more efficiently by BeFX. A chimeric PfAct1 with a mammalian actin D-loop forms a more stable filament. These unusual dynamic properties distinguish PfAct1 from more canonical actins, and likely contribute to the difficultly in visualizing PfAct1 filaments in the parasite. [ABSTRACT FROM AUTHOR]

Published
2019
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115. Myosin II Head Interaction in Primitive Species

Author

Lee, Kyounghwan, primary, Yang, Shixin, additional, Liu, Xiong, additional, Korn, Edward D., additional, Sarsoza, Floyd, additional, Bernstein, Sanford I., additional, Pollard, Luther, additional, Lord, Matthew J., additional, Trybus, Kathleen M., additional, and Craig, Roger, additional

Published
2016
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118. Vascular disease-causing mutation, smooth muscle α-actin R258C, dominantly suppresses functions of α-actin in human patient fibroblasts.

Author

Zhenan Liu, Chang, Audrey N., Grinnell, Frederick, Trybus, Kathleen M., Milewicz, Dianna M., Stull, James T., and Kamm, Kristine E.

Subjects
VASCULAR diseases, GENETIC mutation, SMOOTH muscle, FIBROBLASTS, MOYAMOYA disease
Abstract

The most common genetic alterations for familial thoracic aortic aneurysms and dissections (TAAD) are missense mutations in vascular smooth muscle (SM) α-actin encoded by ACTA2. We focus here on ACTA2-R258C, a recurrent mutation associated with early onset of TAAD and occlusive moyamoya-like cerebrovascular disease. Recent biochemical results with SM α-actin-R258C predicted that this variant will compromise multiple actin-dependent functions in intact cells and tissues, but a model system to measure R258C-induced effects was lacking. We describe the development of an approach to interrogate functional consequences of actin mutations in affected patient-derived cells. Primary dermal fibroblasts from R258C patients exhibited increased proliferative capacity compared with controls, consistent with inhibition of growth suppression attributed to SM α-actin. Telomeraseimmortalized lines of control and R258C human dermal fibroblasts were established and SM α-actin expression induced with adenovirus encoding myocardin-related transcription factor A, a potent coactivator of ACTA2. Two-dimensional Western blotting confirmed induction of both wild-type and mutant SM α-actin in heterozygous ACTA2-R258C cells. Expression of mutant SM α-actin in heterozygous ACTA2-R258C fibroblasts abrogated the significant effects of SM α-actin induction on formation of stress fibers and focal adhesions, filamentous to soluble actin ratio, matrix contraction, and cell migration. These results demonstrate that R258C dominantly disrupts cytoskeletal functions attributed to SM α-actin in fibroblasts and are consistent with deficiencies in multiple cytoskeletal functions. Thus, cellular defects due to this ACTA2 mutation in both aortic smooth muscle cells and adventitial fibroblasts may contribute to development of TAAD and proliferative occlusive vascular disease. [ABSTRACT FROM AUTHOR]

Published
2017
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123. Motor Domain Phosphorylation Modulates Kinesin-1 Transport

Author

DeBerg, Hannah A., primary, Blehm, Benjamin H., additional, Sheung, Janet, additional, Thompson, Andrew R., additional, Bookwalter, Carol S., additional, Torabi, Seyed F., additional, Schroer, Trina A., additional, Berger, Christopher L., additional, Lu, Yi, additional, Trybus, Kathleen M., additional, and Selvin, Paul R., additional

Published
2013
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124. Alpha-cardiac actin mutations produce atrial septal defects.

Author

UCL - MD/BICL - Département de biochimie et de biologie cellulaire, Matsson, Hans, Eason, Jacqueline, Bookwalter, Carol S, Klar, Joakim, Gustavsson, Peter, Sunnegårdh, Jan, Enell, Henrik, Jonzon, Anders, Vikkula, Miikka, Gutierrez-Roelens, Ilse, Granados-Riveron, Javier, Pope, Mark, Bu'Lock, Frances, Cox, Jane, Robinson, Thelma E, Song, Feifei, Brook, David J, Marston, Steven, Trybus, Kathleen M, Dahl, Niklas, UCL - MD/BICL - Département de biochimie et de biologie cellulaire, Matsson, Hans, Eason, Jacqueline, Bookwalter, Carol S, Klar, Joakim, Gustavsson, Peter, Sunnegårdh, Jan, Enell, Henrik, Jonzon, Anders, Vikkula, Miikka, Gutierrez-Roelens, Ilse, Granados-Riveron, Javier, Pope, Mark, Bu'Lock, Frances, Cox, Jane, Robinson, Thelma E, Song, Feifei, Brook, David J, Marston, Steven, Trybus, Kathleen M, and Dahl, Niklas

Abstract

Atrial septal defect (ASD) is one of the most frequent congenital heart defects (CHDs) with a variable phenotypic effect depending on the size of the septal shunt. We identified two pedigrees comprising 20 members segregating isolated autosomal dominant secundum ASD. By genetic mapping, we identified the gene-encoding alpha-cardiac actin (ACTC1), which is essential for cardiac contraction, as the likely candidate. A mutation screen of the coding regions of ACTC1 revealed a founder mutation predicting an M123V substitution in affected individuals of both pedigrees. Functional analysis of ACTC1 with an M123V substitution shows a reduced affinity for myosin, but with retained actomyosin motor properties. We also screened 408 sporadic patients with CHDs and identified a case with ASD and a 17-bp deletion in ACTC1 predicting a non-functional protein. Morpholino (MO) knockdown of ACTC1 in chick embryos produces delayed looping and reduced atrial septa, supporting a developmental role for this protein. The combined results indicate, for the first time, that ACTC1 mutations or reduced ACTC1 levels may lead to ASD without signs of cardiomyopathy.

Published
2008

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