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Structure and Function of Filamin C in the Muscle Z-Disc
Filamin C (FLNC) is one of three filamin proteins (Filamin A (FLNA), Filamin B (FLNB), and FLNC) that cross-link actin filaments and interact with numerous binding partners. FLNC consists of a N-terminal actin-binding domain followed by 24 immunoglobulin-like repeats with two intervening calpain-sen...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216277/ https://www.ncbi.nlm.nih.gov/pubmed/32295012 http://dx.doi.org/10.3390/ijms21082696 |
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author | Mao, Zhenfeng Nakamura, Fumihiko |
author_facet | Mao, Zhenfeng Nakamura, Fumihiko |
author_sort | Mao, Zhenfeng |
collection | PubMed |
description | Filamin C (FLNC) is one of three filamin proteins (Filamin A (FLNA), Filamin B (FLNB), and FLNC) that cross-link actin filaments and interact with numerous binding partners. FLNC consists of a N-terminal actin-binding domain followed by 24 immunoglobulin-like repeats with two intervening calpain-sensitive hinges separating R15 and R16 (hinge 1) and R23 and R24 (hinge-2). The FLNC subunit is dimerized through R24 and calpain cleaves off the dimerization domain to regulate mobility of the FLNC subunit. FLNC is localized in the Z-disc due to the unique insertion of 82 amino acid residues in repeat 20 and necessary for normal Z-disc formation that connect sarcomeres. Since phosphorylation of FLNC by PKC diminishes the calpain sensitivity, assembly, and disassembly of the Z-disc may be regulated by phosphorylation of FLNC. Mutations of FLNC result in cardiomyopathy and muscle weakness. Although this review will focus on the current understanding of FLNC structure and functions in muscle, we will also discuss other filamins because they share high sequence similarity and are better characterized. We will also discuss a possible role of FLNC as a mechanosensor during muscle contraction. |
format | Online Article Text |
id | pubmed-7216277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72162772020-05-22 Structure and Function of Filamin C in the Muscle Z-Disc Mao, Zhenfeng Nakamura, Fumihiko Int J Mol Sci Review Filamin C (FLNC) is one of three filamin proteins (Filamin A (FLNA), Filamin B (FLNB), and FLNC) that cross-link actin filaments and interact with numerous binding partners. FLNC consists of a N-terminal actin-binding domain followed by 24 immunoglobulin-like repeats with two intervening calpain-sensitive hinges separating R15 and R16 (hinge 1) and R23 and R24 (hinge-2). The FLNC subunit is dimerized through R24 and calpain cleaves off the dimerization domain to regulate mobility of the FLNC subunit. FLNC is localized in the Z-disc due to the unique insertion of 82 amino acid residues in repeat 20 and necessary for normal Z-disc formation that connect sarcomeres. Since phosphorylation of FLNC by PKC diminishes the calpain sensitivity, assembly, and disassembly of the Z-disc may be regulated by phosphorylation of FLNC. Mutations of FLNC result in cardiomyopathy and muscle weakness. Although this review will focus on the current understanding of FLNC structure and functions in muscle, we will also discuss other filamins because they share high sequence similarity and are better characterized. We will also discuss a possible role of FLNC as a mechanosensor during muscle contraction. MDPI 2020-04-13 /pmc/articles/PMC7216277/ /pubmed/32295012 http://dx.doi.org/10.3390/ijms21082696 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Mao, Zhenfeng Nakamura, Fumihiko Structure and Function of Filamin C in the Muscle Z-Disc |
title | Structure and Function of Filamin C in the Muscle Z-Disc |
title_full | Structure and Function of Filamin C in the Muscle Z-Disc |
title_fullStr | Structure and Function of Filamin C in the Muscle Z-Disc |
title_full_unstemmed | Structure and Function of Filamin C in the Muscle Z-Disc |
title_short | Structure and Function of Filamin C in the Muscle Z-Disc |
title_sort | structure and function of filamin c in the muscle z-disc |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216277/ https://www.ncbi.nlm.nih.gov/pubmed/32295012 http://dx.doi.org/10.3390/ijms21082696 |
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