The giant isoforms of nesprins 1 and 2 are emerging as important players in cellular organization, particularly in the positioning of nuclei, and possibly other organelles, within the cytoplasm. The experimental evidence suggests that nesprins also occur at the inner nuclear membrane, where they interact with the nuclear lamina. In this paper, we consider whether this is consistent with current ideas about nesprin anchorage and about mechanisms for nuclear import of membrane proteins.
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Unraveling the nexus of nesprin in dilated cardiomyopathy: From molecular insights to therapeutic prospects.
Life Sci
December 2024
Department of Cardiology, Yichang Central People's Hospital/The First Clinical Medical College, Three Gorges University, Yichang 443003, Hubei, People's Republic of China; King's College London British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, London SE5 9NU, UK. Electronic address:
Article Synopsis
- Dilated cardiomyopathy is a serious heart condition where the heart chambers enlarge and weaken, causing difficulty in pumping blood and heart failure.
- Nesprins, which are proteins that connect the nuclear envelope and cytoskeleton, are important for maintaining heart muscle structure and function, especially in the context of dilated cardiomyopathy.
- Mutations in genes related to Nesprin-1 and Nesprin-2 have been linked to this heart disorder, suggesting their critical role in cardiac health and potential targets for new treatments.
Common Genetic Variant Associated With Atrial Fibrillation Lowers Expression of Nesprin-2α1 With Downstream Effects on Nuclear and Electrophysiological Traits.
Circ Genom Precis Med
October 2024
Departments of Cardiovascular and Metabolic Sciences, Cardiovascular Medicine, OH (N.L., J.H., S.V.N.P., D.R.V.W., M.K.C., J.D.S.).
Background: Atrial fibrillation GWAS (genome-wide association studies) identified significant associations for rs1152591 and linked variants in the gene encoding Nesprin-2, which connects the nuclear membrane with the cytoskeleton.
Methods: Reporter gene vector transfection and CRISPR-Cas9 editing were used to identify the causal variant regulating the expression of . After knockdown or overexpression in human stem cell-derived cardiomyocytes, nuclear phenotypes were assessed by imaging and atomic force microscopy.
A distinct isoform of Msp300 (nesprin) organizes the perinuclear microtubule organizing center in adipocytes.
bioRxiv
December 2024
Department of Biomedical Sciences, Florida State University, Tallahassee, FL, USA.
In many cell types, disparate non-centrosomal microtubule-organizing centers (ncMTOCs) replace functional centrosomes and serve the unique needs of the cell types in which they are formed. In Drosophila fat body cells (adipocytes), an ncMTOC is organized on the nuclear surface. This perinuclear ncMTOC is anchored by Msp300, encoded by one of two nesprin-encoding genes in Drosophila.
View Article and Find Full Text PDFNesprin-2 is a novel scaffold protein for telethonin and FHL-2 in the cardiomyocyte sarcomere.
J Biol Chem
May 2024
King's College London British Heart Foundation Centre of Research Excellence, School of Cardiovascular and Metabolic Medicine & Sciences, London, UK. Electronic address:
Article Synopsis
- Nesprins are proteins that connect the nucleoskeleton and cytoskeleton, important for muscle function, and mutations in nesprin-1/-2 are linked to muscular dystrophy and heart conditions.
- Specific nesprin-2 isoforms are found in cardiac muscle, particularly at the sarcomere, indicating a possible role in muscle structure.
- Nesprin-2 interacts with other proteins, like telethonin, which is affected by mutations linked to heart diseases, suggesting nesprin-2 helps maintain muscle integrity and function.
FHODs: Nuclear tethered formins for nuclear mechanotransduction.
Front Cell Dev Biol
May 2023
1 Department of Pathology and Cell Biology, Columbia University, New York, NY, United States.
In this review, we discuss FHOD formins with a focus on recent studies that reveal a new role for them as critical links for nuclear mechanotransduction. The FHOD family in vertebrates comprises two structurally related proteins, FHOD1 and . Their similar biochemical properties suggest overlapping and redundant functions.
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