Dittmar Labeit

CCDC141 is a Connectin/Titin and Nesprin-1 binding protein that adapts cardiomyocytes to mechanical stress

Akira Hanashima, Misaki Kimoto, Yoshihiro Ujihara, Ken Hashimoto et autres

The heart adapts to mechanical stresses such as hypertension, yet the underlying mechanisms remain poorly understood. We identify CCDC141 as a mechanoadaptive factor in cardiomyocytes. CCDC141 interacts with the sarcomeric connectin/titin filament system and the nuclear envelope protein nesprin-1, and localizes to …

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Small‐molecule‐mediated chemical knock‐down of MuRF1/MuRF2 and attenuation of diaphragm dysfunction in chronic heart failure

Volker Adams, Thomas Scott Bowen, Sarah Werner, Peggy Barthel et autres

BACKGROUND: Chronic heart failure (CHF) leads to diaphragm myopathy that significantly impairs quality of life and worsens prognosis. In this study, we aimed to assess the efficacy of a recently discovered small-molecule inhibitor of MuRF1 in treating CHF-induced diaphragm myopathy and loss …

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Titin Gene ( TTN ): Description of the Gene Coding for Titin, a Giant Protein of Critical Importance for Myofibrillar Integrity and Elasticity in Vertebrate Striated Muscle

Siegfried Labeit, Dittmar Labeit, Henk L. M. Granzier

Abstract Up to 34 350 residues long, titin is the largest protein described to date. The titin locus in human located on chromosome 2q24 expresses up to 100 kb (kilobase) full‐length mRNAs (messenger ribonucleic acid) that are translated into giant polypeptides. Titin …

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Small‐molecule inhibition of MuRF1 attenuates skeletal muscle atrophy and dysfunction in cardiac cachexia

Thomas Scott Bowen, Volker Adams, Sarah Werner, Tina Fischer et autres

BACKGROUND: Muscle ring finger 1 (MuRF1) is a muscle-specific ubiquitin E3 ligase activated during clinical conditions associated with skeletal muscle wasting. Yet, there remains a paucity of therapeutic interventions that directly inhibit MuRF1 function, particularly in vivo. The current study, therefore, developed …

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Cardiac specific titin N2B exon is a novel sensitive serological marker for cardiac injury

Julius Bogomolovas, Alexander Gasch, Vilhelmas Bajoras, Dovilė Karčiauskaitė et autres

Cardiovascular diseases are globally a major cause of mortality, with myocardial infarction (MI) presenting as the most frequent acute clinical finding. Early diagnosis is key component for the effective treatment and management of this malady. Modern diagnosis of MI relies on the …

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Sympathetic innervation controls homeostasis of neuromuscular junctions in health and disease

Muzamil Majid Khan, Danilo Lustrino, Wilian Assis Silveira, Franziska Wild et autres

The distribution and function of sympathetic innervation in skeletal muscle have largely remained elusive. Here we demonstrate that sympathetic neurons make close contact with neuromuscular junctions and form a network in skeletal muscle that may functionally couple different targets including blood vessels, …

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A Novel Murine Model of Parvovirus Associated Dilated Cardiomyopathy Induced by Immunization with VP1-Unique Region of Parvovirus B19

Julius Bogomolovas, Egidijus Šimoliūnas, Ieva Rinkūnaitė, Luka Smalinskaitė et autres

Background. Parvovirus B19 (B19V) is a common finding in endomyocardial biopsy specimens from myocarditis and dilated cardiomyopathy patients. However, current understanding of how B19V is contributing to cardiac damage is rather limited due to the lack of appropriate mice models. In this …

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PNAS-2016-Khan-1524272113

Muzamil Majid Khan, Danilo Lustrino, Franziska Wild, Tatjana Straka et autres

Role of autophagy, SQSTM1, SH3GLB1, and TRIM63 in the turnover of nicotinic acetylcholine receptors

Muzamil Majid Khan, Siegfried Strack, Franziska Wild, Akira Hanashima et autres

Removal of ubiquitinated targets by autophagosomes can be mediated by receptor molecules, like SQSTM1, in a mechanism referred to as selective autophagy. While cytoplasmic protein aggregates, mitochondria, and bacteria are the best-known targets of selective autophagy, their role in the turnover of …

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Regulation of nicotinic acetylcholine receptor turnover by MuRF1 connects muscle activity to endo/lysosomal and atrophy pathways

Rüdiger Rudolf, Julius Bogomolovas, Siegfried Strack, Kyeong Rok Choi et autres

Muscle atrophy is a process of muscle wasting induced under a series of catabolic stress conditions, such as denervation, disuse, cancer cachexia, heart and renal failure, AIDS, and aging. Neuromuscular junctions (NMJs), the synapses between motor neurons and muscle fibers undergo major …

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Modulation of Muscle Atrophy, Fatigue and MLC Phosphorylation by MuRF1 as Indicated by Hindlimb Suspension Studies on MuRF1-KO Mice

Siegfried Labeit, Christine Kohl, Christian Witt, Dittmar Labeit et autres

MuRF1 is a member of the TRIM/RBCC superfamily, a gene family that encompasses a large variety of proteins, all sharing the conserved TRIM (Tripartite Motive) sequential array of RING, B-box, and coiled-coil domains. Within this family, MuRF1(also named TRIM63) is a specialized …

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MuRF1-dependent Regulation of Systemic Carbohydrate Metabolism as Revealed from Transgenic Mouse Studies

Stephanie Hirner, Christian Krohne, Alexander Schuster, Sigrid Hoffmann et autres

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