Calpain-6 deficiency promotes skeletal muscle development and regeneration.
Calpains are Ca(2+)-dependent modulator Cys proteases that have a variety of functions in almost all eukaryotes. There are more than 10 well-conserved mammalian calpains, among which eutherian calpain-6 (CAPN6) is unique in that it has amino acid substitutions at the active-site Cys residue (to Lys...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2013-01-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC3731218?pdf=render |
| _version_ | 1818413756175089664 |
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| author | Kazuo Tonami Shoji Hata Koichi Ojima Yasuko Ono Yukiko Kurihara Tomokazu Amano Takahiro Sato Yumiko Kawamura Hiroki Kurihara Hiroyuki Sorimachi |
| author_facet | Kazuo Tonami Shoji Hata Koichi Ojima Yasuko Ono Yukiko Kurihara Tomokazu Amano Takahiro Sato Yumiko Kawamura Hiroki Kurihara Hiroyuki Sorimachi |
| author_sort | Kazuo Tonami |
| collection | DOAJ |
| description | Calpains are Ca(2+)-dependent modulator Cys proteases that have a variety of functions in almost all eukaryotes. There are more than 10 well-conserved mammalian calpains, among which eutherian calpain-6 (CAPN6) is unique in that it has amino acid substitutions at the active-site Cys residue (to Lys in humans), strongly suggesting a loss of proteolytic activity. CAPN6 is expressed predominantly in embryonic muscles, placenta, and several cultured cell lines. We previously reported that CAPN6 is involved in regulating microtubule dynamics and actin reorganization in cultured cells. The physiological functions of CAPN6, however, are still unclear. Here, to elucidate CAPN6's in vivo roles, we generated Capn6-deficient mice, in which a lacZ expression cassette was integrated into the Capn6 gene. These Capn6-deficient mouse embryos expressed lacZ predominantly in skeletal muscles, as well as in cartilage and the heart. Histological and biochemical analyses showed that the CAPN6 deficiency promoted the development of embryonic skeletal muscle. In primary cultured skeletal muscle cells that were induced to differentiate into myotubes, Capn6 expression was detected in skeletal myocytes, and Capn6-deficient cultures showed increased differentiation. Furthermore, we found that CAPN6 was expressed in the regenerating skeletal muscles of adult mice after cardiotoxin-induced degeneration. In this experimental system, Capn6-deficient mice exhibited more advanced skeletal-muscle regeneration than heterozygotes or wild-type mice at the same time point. These results collectively showed that a loss of CAPN6 promotes skeletal muscle differentiation during both development and regeneration, suggesting a novel physiological function of CAPN6 as a suppressor of skeletal muscle differentiation. |
| first_indexed | 2024-12-14T11:08:15Z |
| format | Article |
| id | doaj.art-7744e534724b4e34bb3cd6699b0ae150 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-14T11:08:15Z |
| publishDate | 2013-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-7744e534724b4e34bb3cd6699b0ae1502022-12-21T23:04:26ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042013-01-0198e100366810.1371/journal.pgen.1003668Calpain-6 deficiency promotes skeletal muscle development and regeneration.Kazuo TonamiShoji HataKoichi OjimaYasuko OnoYukiko KuriharaTomokazu AmanoTakahiro SatoYumiko KawamuraHiroki KuriharaHiroyuki SorimachiCalpains are Ca(2+)-dependent modulator Cys proteases that have a variety of functions in almost all eukaryotes. There are more than 10 well-conserved mammalian calpains, among which eutherian calpain-6 (CAPN6) is unique in that it has amino acid substitutions at the active-site Cys residue (to Lys in humans), strongly suggesting a loss of proteolytic activity. CAPN6 is expressed predominantly in embryonic muscles, placenta, and several cultured cell lines. We previously reported that CAPN6 is involved in regulating microtubule dynamics and actin reorganization in cultured cells. The physiological functions of CAPN6, however, are still unclear. Here, to elucidate CAPN6's in vivo roles, we generated Capn6-deficient mice, in which a lacZ expression cassette was integrated into the Capn6 gene. These Capn6-deficient mouse embryos expressed lacZ predominantly in skeletal muscles, as well as in cartilage and the heart. Histological and biochemical analyses showed that the CAPN6 deficiency promoted the development of embryonic skeletal muscle. In primary cultured skeletal muscle cells that were induced to differentiate into myotubes, Capn6 expression was detected in skeletal myocytes, and Capn6-deficient cultures showed increased differentiation. Furthermore, we found that CAPN6 was expressed in the regenerating skeletal muscles of adult mice after cardiotoxin-induced degeneration. In this experimental system, Capn6-deficient mice exhibited more advanced skeletal-muscle regeneration than heterozygotes or wild-type mice at the same time point. These results collectively showed that a loss of CAPN6 promotes skeletal muscle differentiation during both development and regeneration, suggesting a novel physiological function of CAPN6 as a suppressor of skeletal muscle differentiation.http://europepmc.org/articles/PMC3731218?pdf=render |
| spellingShingle | Kazuo Tonami Shoji Hata Koichi Ojima Yasuko Ono Yukiko Kurihara Tomokazu Amano Takahiro Sato Yumiko Kawamura Hiroki Kurihara Hiroyuki Sorimachi Calpain-6 deficiency promotes skeletal muscle development and regeneration. PLoS Genetics |
| title | Calpain-6 deficiency promotes skeletal muscle development and regeneration. |
| title_full | Calpain-6 deficiency promotes skeletal muscle development and regeneration. |
| title_fullStr | Calpain-6 deficiency promotes skeletal muscle development and regeneration. |
| title_full_unstemmed | Calpain-6 deficiency promotes skeletal muscle development and regeneration. |
| title_short | Calpain-6 deficiency promotes skeletal muscle development and regeneration. |
| title_sort | calpain 6 deficiency promotes skeletal muscle development and regeneration |
| url | http://europepmc.org/articles/PMC3731218?pdf=render |
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