Metadata language
Wojton, Dominika Anna (1994– )
Institutional creator:Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN.
Contributor:Rędowicz, Maria Jolanta (1959– ) : Supervisor ; Lehka, Liliia : Auxiliary supervisor
Publisher:Instytut Biologii Doświadczalnej im. Marcelego Nenckiego PAN
Place of publishing: Date issued/created: Description:122 pages : illustrations ; 30 cm ; Bibliography ; Summary in English
Degree name: Degree discipline : Degree grantor:Nencki Institute of Experimental Biology PAS ; degree obtained: 27.06.2025
Type of object: Subject and Keywords:Myosin VI ; Skeletal muscle ; Metabolism ; Lipolysis ; Mitochondria ; Muscle fiber
Abstract:
Myosin VI (MVI) is a member of the myosin superfamily, which consists of over 35 structurally and functionally diverse families, with representatives found in nearly all eukaryotic organisms. It is the only unconventional (i.e. not forming filaments) myosin that moves toward the “minus” end of actin filament. This molecular motor is involved in numerous cellular processes such as endo-and exocytosis, gene transcription, cell migration, maintenance of the Golgi apparatus, adhesion, and autophagy. Its wide range of cellular functions is possible through interactions with various binding partners within multi-protein complexes. Mutations in the Myo6 gene lead to hearing loss and hypertrophic cardiomyopathy. Professor Rędowicz's team was the first to demonstrate that MVI is also present in skeletal muscles where it localizes to the postsynaptic region of the neuromuscular junction, the sarcoplasmic reticulum and myonuclei. Additionally, our group demonstrated that the absence of MVI disrupts the mechanisms responsible for cytoskeleton organization, as well as myoblast adhesion and fusion. Moreover, we also showed that the muscle-to-body mass ratio is increased in mice lacking MVI. Based on these observations, I aimed to deepen the understanding of the role of MVI in skeletal muscles. I performed my study using Snell’s waltzer mice (SV, MVI-KO), which are considered as natural MVI knockout due to a spontaneous recessive mutation in the Myo6 that prevents the synthesis of functional MVI. MVI-KO mice are deaf and exhibit hyperactivity, circling and head tossing. I examined the hindlimb muscle from newborn (P0) as well as 3-, and 12-month old mice. Heterozygous littermates were the control, referred to in this study as WT. I have shown that MVI mRNA and protein synthesis is the highest in muscles of newborn mice and significantly decreases with age. Furthermore, MVI transcript and protein levels are muscle-type dependent, with the highest amount observed in the slow-twitch soleus muscle (SOL) of adult mice. Loss or depletion of MVI leads to a significant impairment of the respiratory capacity of myogenic cells. This was accompanied by lower levels of ATP in both myogenic cells and skeletal muscles. Moreover, I observed differences in the activity of the cAMP/PKA and AMPK/mTOR pathways in the skeletal muscles of MVI-KO mice. Alterations in these key metabolic pathways were associated with activation of lipolysis and a transition from glycolytic to oxidative fiber types in muscles of MVI-KO mice. In addition, the absence of MVI also resulted in changes in myofibers morphology as I noticed lower values of the cross- sectional area of muscle fibers and their higher number. In summary, this dissertation presents a data indicating a novel role of MVI in the functioning of skeletal muscles. My findings indicate that MVI is involved in the maintenance of the myofiber morphology and regulation of skeletal muscle metabolism.
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Copyright holder:Publication made available with the written permission of the author
Digitizing institution:Nencki Institute of Experimental Biology of the Polish Academy of Sciences
Original in:Library of the Nencki Institute of Experimental Biology PAS
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