Myosin VI depletion delays neuromuscular junction maturation and exacerbates muscle performance

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Publicat a:Scientific Reports (Nature Publisher Group) vol. 15, no. 1 (2025), p. 44863-44876
Autor principal: Nowak, Jolanta
Altres autors: Alvarez-Suarez, Paloma, Włodarczyk, Tomasz, Zakrzewska, Renata, Boguszewski, Paweł Marek, Rędowicz, Maria Jolanta, Gawor, Marta
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100 1 |a Nowak, Jolanta  |u Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland (ROR: https://ror.org/04waf7p94) (GRID: grid.419305.a) (ISNI: 0000 0001 1943 2944) 
245 1 |a Myosin VI depletion delays neuromuscular junction maturation and exacerbates muscle performance 
260 |b Nature Publishing Group  |c 2025 
513 |a Journal Article 
520 3 |a Unconventional myosin VI (MVI) is an ATP-dependent actin-binding molecular motor that participates in numerous cellular and tissue functions, including striated muscle physiology. Lack of MVI expression significantly aberrates myogenesis and skeletal muscle metabolism, and alters myoblast adhesion, fusion, and cytoskeletal organisation. Concomitantly, MVI knockout mice display functional and structural cardiac defects. Here, for the first time, we investigate the impact of MVI on neuromuscular junctions (NMJs), the peripheral synapses crucial for skeletal muscle contraction. We show that MVI is enriched at the postsynaptic machinery of developing and adult NMJs. We analyse the morphology of NMJs of MVI knockout mice (Snell’s waltzer, SV) during early developmental remodelling and show that MVI deficiency delays NMJ maturation in fast- and slow-twitch muscles. It also reduces the NMJ size of the soleus muscle, as demonstrated by the decreased morphological parameters of both presynaptic and postsynaptic compartments. Simultaneously, synaptic elimination remains unaffected after MVI knockout, suggesting that the observed phenotypes are innervation-independent. Lastly, depletion of MVI impairs the grip strength of both female and male SV/SV mice. In summary, our studies show that MVI is an important regulator of NMJ size and maturation, controls muscle performance, and its impact is independent of innervation and sex. 
653 |a Myoblasts 
653 |a Myogenesis 
653 |a Soleus muscle 
653 |a Maturation 
653 |a Musculoskeletal system 
653 |a Skeletal muscle 
653 |a Myosin 
653 |a Actin 
653 |a Neuromuscular junctions 
653 |a Phenotypes 
653 |a Cytoskeleton 
653 |a Muscle contraction 
653 |a Muscles 
653 |a Muscle function 
653 |a Localization 
653 |a Structure-function relationships 
653 |a Innervation 
653 |a Morphology 
653 |a Adults 
653 |a Proteins 
653 |a Environmental 
700 1 |a Alvarez-Suarez, Paloma  |u Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland (ROR: https://ror.org/04waf7p94) (GRID: grid.419305.a) (ISNI: 0000 0001 1943 2944) 
700 1 |a Włodarczyk, Tomasz  |u Laboratory of Behavioral Methods, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland (ROR: https://ror.org/04waf7p94) (GRID: grid.419305.a) (ISNI: 0000 0001 1943 2944) 
700 1 |a Zakrzewska, Renata  |u Laboratory of Behavioral Methods, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland (ROR: https://ror.org/04waf7p94) (GRID: grid.419305.a) (ISNI: 0000 0001 1943 2944) 
700 1 |a Boguszewski, Paweł Marek  |u Laboratory of Behavioral Methods, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland (ROR: https://ror.org/04waf7p94) (GRID: grid.419305.a) (ISNI: 0000 0001 1943 2944) 
700 1 |a Rędowicz, Maria Jolanta  |u Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland (ROR: https://ror.org/04waf7p94) (GRID: grid.419305.a) (ISNI: 0000 0001 1943 2944) 
700 1 |a Gawor, Marta  |u Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur Street, 02-093, Warsaw, Poland (ROR: https://ror.org/04waf7p94) (GRID: grid.419305.a) (ISNI: 0000 0001 1943 2944) 
773 0 |t Scientific Reports (Nature Publisher Group)  |g vol. 15, no. 1 (2025), p. 44863-44876 
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