Identification of Novel Nexilin Splice Variants in Mouse and Human Tissues

There is no doubt that the proper development of the heart is important for its correct function, in addition, maturation processes of the heart are crucial as well. The actin-binding protein nexilin seems to take over central roles in the latter processes, as nexilin-deficient mice are phenotypical...

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Main Authors: Paul Jung, André Fiedelak, Celina Dreeßen, Otmar Huber, Juliane Reiche
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/13/23/2018
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author Paul Jung
André Fiedelak
Celina Dreeßen
Otmar Huber
Juliane Reiche
author_facet Paul Jung
André Fiedelak
Celina Dreeßen
Otmar Huber
Juliane Reiche
author_sort Paul Jung
collection DOAJ
description There is no doubt that the proper development of the heart is important for its correct function, in addition, maturation processes of the heart are crucial as well. The actin-binding protein nexilin seems to take over central roles in the latter processes, as nexilin-deficient mice are phenotypically inconspicuous at birth but die within short time thereafter. Recently, it has been proposed that nexilin plays a role in the formation and function of transverse tubules (T-tubules), which are essential for excitation-contraction coupling in the hearts of mature animals. Although it has long been known that nexilin is subjected to alternative splicing, a molecular characterization of the respective isoforms is not yet available. Here, we describe novel nexilin splice variants and analyze their expression in tissues of mice and humans. Interestingly, nexilin isoforms segregate to myocyte- and epithelial-specific isoforms. Moreover, heart-specific isoforms of nexilin localize differently between atria and ventricles and are also expressed in the endothelial cells of blood vessels. Further, we narrowed down the critical exons in the actin-binding domains 1 and 2 (ABD1/2), and observed different self-interaction properties by recombinant protein interaction studies. Our results emphasize the diverse tissue and subcellular distribution of the individual nexilin isoforms and point to the importance of taking a closer look at the particular nexilin isoforms investigated.
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spelling doaj-art-3c67d2e7c3df4e87b8d840bb92b27cbd2025-08-20T02:38:47ZengMDPI AGCells2073-44092024-12-011323201810.3390/cells13232018Identification of Novel Nexilin Splice Variants in Mouse and Human TissuesPaul Jung0André Fiedelak1Celina Dreeßen2Otmar Huber3Juliane Reiche4Institute of Biochemistry II, Jena University Hospital, Friedrich Schiller University Jena, Nonnenplan 2-4, 07743 Jena, GermanyInstitute of Biochemistry II, Jena University Hospital, Friedrich Schiller University Jena, Nonnenplan 2-4, 07743 Jena, GermanyInstitute of Biochemistry II, Jena University Hospital, Friedrich Schiller University Jena, Nonnenplan 2-4, 07743 Jena, GermanyInstitute of Biochemistry II, Jena University Hospital, Friedrich Schiller University Jena, Nonnenplan 2-4, 07743 Jena, GermanyInstitute of Biochemistry II, Jena University Hospital, Friedrich Schiller University Jena, Nonnenplan 2-4, 07743 Jena, GermanyThere is no doubt that the proper development of the heart is important for its correct function, in addition, maturation processes of the heart are crucial as well. The actin-binding protein nexilin seems to take over central roles in the latter processes, as nexilin-deficient mice are phenotypically inconspicuous at birth but die within short time thereafter. Recently, it has been proposed that nexilin plays a role in the formation and function of transverse tubules (T-tubules), which are essential for excitation-contraction coupling in the hearts of mature animals. Although it has long been known that nexilin is subjected to alternative splicing, a molecular characterization of the respective isoforms is not yet available. Here, we describe novel nexilin splice variants and analyze their expression in tissues of mice and humans. Interestingly, nexilin isoforms segregate to myocyte- and epithelial-specific isoforms. Moreover, heart-specific isoforms of nexilin localize differently between atria and ventricles and are also expressed in the endothelial cells of blood vessels. Further, we narrowed down the critical exons in the actin-binding domains 1 and 2 (ABD1/2), and observed different self-interaction properties by recombinant protein interaction studies. Our results emphasize the diverse tissue and subcellular distribution of the individual nexilin isoforms and point to the importance of taking a closer look at the particular nexilin isoforms investigated.https://www.mdpi.com/2073-4409/13/23/2018nexilinheart maturationsplicingisoformF-actinT-tubule
spellingShingle Paul Jung
André Fiedelak
Celina Dreeßen
Otmar Huber
Juliane Reiche
Identification of Novel Nexilin Splice Variants in Mouse and Human Tissues
Cells
nexilin
heart maturation
splicing
isoform
F-actin
T-tubule
title Identification of Novel Nexilin Splice Variants in Mouse and Human Tissues
title_full Identification of Novel Nexilin Splice Variants in Mouse and Human Tissues
title_fullStr Identification of Novel Nexilin Splice Variants in Mouse and Human Tissues
title_full_unstemmed Identification of Novel Nexilin Splice Variants in Mouse and Human Tissues
title_short Identification of Novel Nexilin Splice Variants in Mouse and Human Tissues
title_sort identification of novel nexilin splice variants in mouse and human tissues
topic nexilin
heart maturation
splicing
isoform
F-actin
T-tubule
url https://www.mdpi.com/2073-4409/13/23/2018
work_keys_str_mv AT pauljung identificationofnovelnexilinsplicevariantsinmouseandhumantissues
AT andrefiedelak identificationofnovelnexilinsplicevariantsinmouseandhumantissues
AT celinadreeßen identificationofnovelnexilinsplicevariantsinmouseandhumantissues
AT otmarhuber identificationofnovelnexilinsplicevariantsinmouseandhumantissues
AT julianereiche identificationofnovelnexilinsplicevariantsinmouseandhumantissues