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Alternative Splicing of Pericentrin Contributes to Cell Cycle Control in Cardiomyocytes

Induction of cardiomyocyte proliferation is a promising option to regenerate the heart. Thus, it is important to elucidate mechanisms that contribute to the cell cycle arrest of mammalian cardiomyocytes. Here, we assessed the contribution of the pericentrin (Pcnt) S isoform to cell cycle arrest in p...

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Autores principales: Steinfeldt, Jakob, Becker, Robert, Vergarajauregui, Silvia, Engel, Felix B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397033/
https://www.ncbi.nlm.nih.gov/pubmed/34436229
http://dx.doi.org/10.3390/jcdd8080087
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author Steinfeldt, Jakob
Becker, Robert
Vergarajauregui, Silvia
Engel, Felix B.
author_facet Steinfeldt, Jakob
Becker, Robert
Vergarajauregui, Silvia
Engel, Felix B.
author_sort Steinfeldt, Jakob
collection PubMed
description Induction of cardiomyocyte proliferation is a promising option to regenerate the heart. Thus, it is important to elucidate mechanisms that contribute to the cell cycle arrest of mammalian cardiomyocytes. Here, we assessed the contribution of the pericentrin (Pcnt) S isoform to cell cycle arrest in postnatal cardiomyocytes. Immunofluorescence staining of Pcnt isoforms combined with SiRNA-mediated depletion indicates that Pcnt S preferentially localizes to the nuclear envelope, while the Pcnt B isoform is enriched at centrosomes. This is further supported by the localization of ectopically expressed FLAG-tagged Pcnt S and Pcnt B in postnatal cardiomyocytes. Analysis of centriole configuration upon Pcnt depletion revealed that Pcnt B but not Pcnt S is required for centriole cohesion. Importantly, ectopic expression of Pcnt S induced centriole splitting in a heterologous system, ARPE-19 cells, and was sufficient to impair DNA synthesis in C2C12 myoblasts. Moreover, Pcnt S depletion enhanced serum-induced cell cycle re-entry in postnatal cardiomyocytes. Analysis of mitosis, binucleation rate, and cell number suggests that Pcnt S depletion enhances serum-induced progression of postnatal cardiomyocytes through the cell cycle resulting in cell division. Collectively, our data indicate that alternative splicing of Pcnt contributes to the establishment of cardiomyocyte cell cycle arrest shortly after birth.
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spelling pubmed-83970332021-08-28 Alternative Splicing of Pericentrin Contributes to Cell Cycle Control in Cardiomyocytes Steinfeldt, Jakob Becker, Robert Vergarajauregui, Silvia Engel, Felix B. J Cardiovasc Dev Dis Article Induction of cardiomyocyte proliferation is a promising option to regenerate the heart. Thus, it is important to elucidate mechanisms that contribute to the cell cycle arrest of mammalian cardiomyocytes. Here, we assessed the contribution of the pericentrin (Pcnt) S isoform to cell cycle arrest in postnatal cardiomyocytes. Immunofluorescence staining of Pcnt isoforms combined with SiRNA-mediated depletion indicates that Pcnt S preferentially localizes to the nuclear envelope, while the Pcnt B isoform is enriched at centrosomes. This is further supported by the localization of ectopically expressed FLAG-tagged Pcnt S and Pcnt B in postnatal cardiomyocytes. Analysis of centriole configuration upon Pcnt depletion revealed that Pcnt B but not Pcnt S is required for centriole cohesion. Importantly, ectopic expression of Pcnt S induced centriole splitting in a heterologous system, ARPE-19 cells, and was sufficient to impair DNA synthesis in C2C12 myoblasts. Moreover, Pcnt S depletion enhanced serum-induced cell cycle re-entry in postnatal cardiomyocytes. Analysis of mitosis, binucleation rate, and cell number suggests that Pcnt S depletion enhances serum-induced progression of postnatal cardiomyocytes through the cell cycle resulting in cell division. Collectively, our data indicate that alternative splicing of Pcnt contributes to the establishment of cardiomyocyte cell cycle arrest shortly after birth. MDPI 2021-07-27 /pmc/articles/PMC8397033/ /pubmed/34436229 http://dx.doi.org/10.3390/jcdd8080087 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Steinfeldt, Jakob
Becker, Robert
Vergarajauregui, Silvia
Engel, Felix B.
Alternative Splicing of Pericentrin Contributes to Cell Cycle Control in Cardiomyocytes
title Alternative Splicing of Pericentrin Contributes to Cell Cycle Control in Cardiomyocytes
title_full Alternative Splicing of Pericentrin Contributes to Cell Cycle Control in Cardiomyocytes
title_fullStr Alternative Splicing of Pericentrin Contributes to Cell Cycle Control in Cardiomyocytes
title_full_unstemmed Alternative Splicing of Pericentrin Contributes to Cell Cycle Control in Cardiomyocytes
title_short Alternative Splicing of Pericentrin Contributes to Cell Cycle Control in Cardiomyocytes
title_sort alternative splicing of pericentrin contributes to cell cycle control in cardiomyocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397033/
https://www.ncbi.nlm.nih.gov/pubmed/34436229
http://dx.doi.org/10.3390/jcdd8080087
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