Amyloid Aggregates of Smooth-Muscle Titin Impair Cell Adhesion

Bobylev, A. G.; Фадеев, Р. С.; Bobyleva, L. G.; Kobyakova, M. I.; Shlyapnikov, Yuri M.; Popov, D. V.; Vikhlyantsev, I. M.

doi:10.3390/ijms22094579

Cited by 6 publications

(8 citation statements)

References 74 publications

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“…Based on our previous research into SMT LMW [ 34 , 35 ] and SMT HMW [ 36 ], we were aware of the conditions required to form amyloid aggregates of these proteins. This work, in order to understand the features of chicken titin aggregation rate, investigated the kinetics of SMT HMW aggregation.…”

Section: Resultsmentioning

confidence: 99%

Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations

Bobylev

Yakupova

Bobyleva

et al. 2023

IJMS

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A giant multidomain protein of striated and smooth vertebrate muscles, titin, consists of tandems of immunoglobulin (Ig)- and fibronectin type III (FnIII)-like domains representing β-sandwiches, as well as of disordered segments. Chicken smooth muscles express several titin isoforms of ~500–1500 kDa. Using various structural-analysis methods, we investigated in vitro nonspecific amyloid aggregation of the high-molecular-weight isoform of chicken smooth-muscle titin (SMTHMW, ~1500 kDa). As confirmed by X-ray diffraction analysis, under near-physiological conditions, the protein formed amorphous amyloid aggregates with a quaternary cross-β structure within a relatively short time (~60 min). As shown by circular dichroism and Fourier-transform infrared spectroscopy, the quaternary cross-β structure—unlike other amyloidogenic proteins—formed without changes in the SMTHMW secondary structure. SMTHMW aggregates partially disaggregated upon increasing the ionic strength above the physiological level. Based on the data obtained, it is not the complete protein but its particular domains/segments that are likely involved in the formation of intermolecular interactions during SMTHMW amyloid aggregation. The discovered properties of titin position this protein as an object of interest for studying amyloid aggregation in vitro and expanding our views of the fundamentals of amyloidogenesis.

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Section: Resultsmentioning

confidence: 99%

Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations

Bobylev

Yakupova

Bobyleva

et al. 2023

IJMS

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“…Mislocalization may cause depletion of the NUPs in the envelope, affecting nuclear–cytoplasmic transport. In addition, cytoplasmic aggregation of NUPs could be toxic to cytoplasmic events such as intracellular signaling and maintenance of redox homeostasis ( Rajasekaran et al, 2007 ; Chivet et al, 2020 ; Bobylev et al, 2021 ; Coombs et al, 2021 ; Potulska-Chromik et al, 2021 ). Thus, the mutant lamins had differing effects on NUP localization with several residues in the rod and Ig-like fold domains implicated in proper NUP formation.…”

Section: Resultsmentioning

confidence: 99%

Effects of mutant lamins on nucleo-cytoskeletal coupling in Drosophila models of LMNA muscular dystrophy

Shaw

Rios-Monterrosa

Fedorchak

et al. 2022

Front. Cell Dev. Biol.

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The nuclei of multinucleated skeletal muscles experience substantial external force during development and muscle contraction. Protection from such forces is partly provided by lamins, intermediate filaments that form a scaffold lining the inner nuclear membrane. Lamins play a myriad of roles, including maintenance of nuclear shape and stability, mediation of nuclear mechanoresponses, and nucleo-cytoskeletal coupling. Herein, we investigate how disease-causing mutant lamins alter myonuclear properties in response to mechanical force. This was accomplished via a novel application of a micropipette harpooning assay applied to larval body wall muscles of Drosophila models of lamin-associated muscular dystrophy. The assay enables the measurement of both nuclear deformability and intracellular force transmission between the cytoskeleton and nuclear interior in intact muscle fibers. Our studies revealed that specific mutant lamins increase nuclear deformability while other mutant lamins cause nucleo-cytoskeletal coupling defects, which were associated with loss of microtubular nuclear caging. We found that microtubule caging of the nucleus depended on Msp300, a KASH domain protein that is a component of the linker of nucleoskeleton and cytoskeleton (LINC) complex. Taken together, these findings identified residues in lamins required for connecting the nucleus to the cytoskeleton and suggest that not all muscle disease-causing mutant lamins produce similar defects in subcellular mechanics.

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“…Los mecanismos de toxicidad no han sido completamente entendidos, pero se ha observado que en miocitos lisos alteran la adhesión celular (Bobylev et al, 2021). En el caso de enfermedades neurodegenerativas como el Alzheimer y el Parkinson, la translocación de fibrillas a las membranas celulares puede generar daño mitocondrial y desencadenar la apoptosis (Hashimoto et al, 2003).…”

Section: Composición Características Y Patogeniaunclassified

Amiloidosis sistémica AA: un problema potencial de salud pública

2022

Abanico Vet

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El objetivo de esta revisión es informar a los profesionales en salud animal, sobre la amiloidosis sistémica AA, un problema potencial de salud pública poco conocido en México, que puede derivarse del consumo de productos animales. Es difícil de diagnosticar, pues los signos clínicos dependen del tipo y localización del amiloide; y su fase terminal corresponde con un cuadro de insuficiencia renal. Consiste en la acumulación de un material proteico extracelular que puede originarse a partir de alrededor de 37 proteínas normales en los humanos y más de 15 en otros mamíferos acuáticos y terrestres, y en aves. Posee una estructura fibrilar característica en disposición β plegada que le confiere gran resistencia a agentes fisicoquímicos, que hace difícil su eliminación de los alimentos. Algunas amiloidosis, como el Alzheimer en humanos y el trastorno de disfunción cognitiva en los perros, son localizadas, pero la amiloidosis AA es sistémica y existe evidencia natural y experimental de que puede transmitirse intra e inter-especie cuando hay ingreso por vía oral, intravenosa o intraperitoneal de material amiloide en un individuo con una enfermedad inflamatoria crónica pre-existente u otros factores de riesgo, como la obesidad, lo que la convierte en un potencial problema de salud pública.

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Amyloid Aggregates of Smooth-Muscle Titin Impair Cell Adhesion

Cited by 6 publications

References 74 publications

Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations

Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations

Effects of mutant lamins on nucleo-cytoskeletal coupling in Drosophila models of LMNA muscular dystrophy

Amiloidosis sistémica AA: un problema potencial de salud pública

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