Cargando…

Loss of Unconventional Myosin VI Affects cAMP/PKA Signaling in Hindlimb Skeletal Muscle in an Age-Dependent Manner

Myosin VI (MVI) is a unique unconventional myosin ubiquitously expressed in metazoans. Its diverse cellular functions are mediated by interactions with a number of binding partners present in multi-protein complexes. MVI is proposed to play important roles in muscle function and myogenesis. Previous...

Descripción completa

Detalles Bibliográficos
Autores principales: Lehka, Lilya, Wojton, Dominika, Topolewska, Małgorzata, Chumak, Vira, Majewski, Łukasz, Rędowicz, Maria Jolanta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273875/
https://www.ncbi.nlm.nih.gov/pubmed/35837016
http://dx.doi.org/10.3389/fphys.2022.933963
_version_ 1784745173448654848
author Lehka, Lilya
Wojton, Dominika
Topolewska, Małgorzata
Chumak, Vira
Majewski, Łukasz
Rędowicz, Maria Jolanta
author_facet Lehka, Lilya
Wojton, Dominika
Topolewska, Małgorzata
Chumak, Vira
Majewski, Łukasz
Rędowicz, Maria Jolanta
author_sort Lehka, Lilya
collection PubMed
description Myosin VI (MVI) is a unique unconventional myosin ubiquitously expressed in metazoans. Its diverse cellular functions are mediated by interactions with a number of binding partners present in multi-protein complexes. MVI is proposed to play important roles in muscle function and myogenesis. Previously, we showed that MVI is present in striated muscles and myogenic cells, and MVI interacts with A-kinase anchoring protein 9 (AKAP9), a scaffold for PKA and its regulatory proteins. Since PKA directly phosphorylates the MVI cargo binding domain, we hypothesized that the cellular effects of MVI are mediated by the cAMP/PKA signaling pathway, known to play important roles in skeletal muscle metabolism and myogenesis. To elucidate the potential role of MVI in PKA signaling in hindlimb muscle function, we used mice lacking MVI (Snell’s waltzer, SV), considered as natural MVI knockouts, and heterozygous littermates. We used muscles isolated from newborn (P0) as well as 3- and 12-month-old adult mice. We observed a significant increase in the muscle to body mass ratio, which was most evident for the soleus muscle, as well as changes in fiber size, indicating alterations in muscle metabolism. These observations were accompanied by age-dependent changes in the activity of PKA and cAMP/PKA-dependent transcriptional factor (CREB). Additionally, the levels of adenylate cyclase isoforms and phosphodiesterase (PDE4) were age-dependent. Also, cAMP levels were decreased in the muscle of P0 mice. Together, these observations indicate that lack of MVI impairs PKA signaling and results in the observed alterations in the SV muscle metabolism, in particular in newborn mice.
format Online
Article
Text
id pubmed-9273875
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92738752022-07-13 Loss of Unconventional Myosin VI Affects cAMP/PKA Signaling in Hindlimb Skeletal Muscle in an Age-Dependent Manner Lehka, Lilya Wojton, Dominika Topolewska, Małgorzata Chumak, Vira Majewski, Łukasz Rędowicz, Maria Jolanta Front Physiol Physiology Myosin VI (MVI) is a unique unconventional myosin ubiquitously expressed in metazoans. Its diverse cellular functions are mediated by interactions with a number of binding partners present in multi-protein complexes. MVI is proposed to play important roles in muscle function and myogenesis. Previously, we showed that MVI is present in striated muscles and myogenic cells, and MVI interacts with A-kinase anchoring protein 9 (AKAP9), a scaffold for PKA and its regulatory proteins. Since PKA directly phosphorylates the MVI cargo binding domain, we hypothesized that the cellular effects of MVI are mediated by the cAMP/PKA signaling pathway, known to play important roles in skeletal muscle metabolism and myogenesis. To elucidate the potential role of MVI in PKA signaling in hindlimb muscle function, we used mice lacking MVI (Snell’s waltzer, SV), considered as natural MVI knockouts, and heterozygous littermates. We used muscles isolated from newborn (P0) as well as 3- and 12-month-old adult mice. We observed a significant increase in the muscle to body mass ratio, which was most evident for the soleus muscle, as well as changes in fiber size, indicating alterations in muscle metabolism. These observations were accompanied by age-dependent changes in the activity of PKA and cAMP/PKA-dependent transcriptional factor (CREB). Additionally, the levels of adenylate cyclase isoforms and phosphodiesterase (PDE4) were age-dependent. Also, cAMP levels were decreased in the muscle of P0 mice. Together, these observations indicate that lack of MVI impairs PKA signaling and results in the observed alterations in the SV muscle metabolism, in particular in newborn mice. Frontiers Media S.A. 2022-06-28 /pmc/articles/PMC9273875/ /pubmed/35837016 http://dx.doi.org/10.3389/fphys.2022.933963 Text en Copyright © 2022 Lehka, Wojton, Topolewska, Chumak, Majewski and Rędowicz. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Lehka, Lilya
Wojton, Dominika
Topolewska, Małgorzata
Chumak, Vira
Majewski, Łukasz
Rędowicz, Maria Jolanta
Loss of Unconventional Myosin VI Affects cAMP/PKA Signaling in Hindlimb Skeletal Muscle in an Age-Dependent Manner
title Loss of Unconventional Myosin VI Affects cAMP/PKA Signaling in Hindlimb Skeletal Muscle in an Age-Dependent Manner
title_full Loss of Unconventional Myosin VI Affects cAMP/PKA Signaling in Hindlimb Skeletal Muscle in an Age-Dependent Manner
title_fullStr Loss of Unconventional Myosin VI Affects cAMP/PKA Signaling in Hindlimb Skeletal Muscle in an Age-Dependent Manner
title_full_unstemmed Loss of Unconventional Myosin VI Affects cAMP/PKA Signaling in Hindlimb Skeletal Muscle in an Age-Dependent Manner
title_short Loss of Unconventional Myosin VI Affects cAMP/PKA Signaling in Hindlimb Skeletal Muscle in an Age-Dependent Manner
title_sort loss of unconventional myosin vi affects camp/pka signaling in hindlimb skeletal muscle in an age-dependent manner
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273875/
https://www.ncbi.nlm.nih.gov/pubmed/35837016
http://dx.doi.org/10.3389/fphys.2022.933963
work_keys_str_mv AT lehkalilya lossofunconventionalmyosinviaffectscamppkasignalinginhindlimbskeletalmuscleinanagedependentmanner
AT wojtondominika lossofunconventionalmyosinviaffectscamppkasignalinginhindlimbskeletalmuscleinanagedependentmanner
AT topolewskamałgorzata lossofunconventionalmyosinviaffectscamppkasignalinginhindlimbskeletalmuscleinanagedependentmanner
AT chumakvira lossofunconventionalmyosinviaffectscamppkasignalinginhindlimbskeletalmuscleinanagedependentmanner
AT majewskiłukasz lossofunconventionalmyosinviaffectscamppkasignalinginhindlimbskeletalmuscleinanagedependentmanner
AT redowiczmariajolanta lossofunconventionalmyosinviaffectscamppkasignalinginhindlimbskeletalmuscleinanagedependentmanner