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HACD1, a regulator of membrane composition and fluidity, promotes myoblast fusion and skeletal muscle growth.

Blondelle J, Ohno Y, Gache V, Guyot S, Storck S, Blanchard-Gutton N, Barthélémy I, Walmsley G, Rahier A, Gadin S, Maurer M, Guillaud L, Prola A, Ferry A, Aubin-Houzelstein G, Demarquoy J, Relaix F, Piercy RJ, Blot S, Kihara A, Tiret L, Pilot-Storck F - J Mol Cell Biol (2015)

Bottom Line: We further demonstrate that in normal differentiating myoblasts, expression of the catalytically active HACD1 isoform, which is encoded by a muscle-enriched splice variant, yields decreased lysophosphatidylcholine content, a potent inhibitor of myoblast fusion, and increased concentrations of ≥ C18 and monounsaturated fatty acids of phospholipids.These lipid modifications correlate with a reduction in plasma membrane rigidity.In conclusion, we propose that fusion impairment constitutes a novel, non-exclusive pathological mechanism operating in congenital myopathies and reveal that HACD1 is a key regulator of a lipid-dependent muscle fibre growth mechanism.

View Article: PubMed Central - PubMed

Affiliation: Inserm, IMRB U955-E10, 94000 Créteil, France Université Paris-Est, Ecole nationale vétérinaire d'Alfort (EnvA), 94700 Maisons-Alfort, France Université Paris-Est Créteil, Faculté de médecine, 94000 Créteil, France.

No MeSH data available.


Related in: MedlinePlus

Upregulation of the muscle-specific, Hacd1-full length (Hacd1-fl) isoform during muscle fibre development. (A and B) X-Gal staining of a Hacd1+/− embryo at E12.5 (A), TA muscles (B) from a Hacd1−/− mouse on Day 15 after injection of NaCl (left) or notexin (right). (C) Dissected fibres from the notexin-injected muscle shown in B showing X-Gal staining in a regenerative fibre (centralized nuclei, in blue). Scale bar, 20 μm. (D) RT-PCR experiments showing expression of Hacd1 transcripts in mouse tissues and embryos. (E–H) Expression of Hacd1 transcripts during differentiation of primary muscle cells (E and F) and C2C12 cells (G and H) revealed by RT-PCR experiments (E and G) or RT-qPCR experiments (F and H) showing fold-change from proliferation for each isoform (n = 3 for each condition). (I) RT-qPCR experiments for Hacd1-fl and Hacd1-d5 isoforms in TA muscles from wild-type mice, either non-injected (n = 4) or on Day 6 (n = 3) or Day 15 (n = 4) after notexin injection. Error bars correspond to standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001.
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MJV049F5: Upregulation of the muscle-specific, Hacd1-full length (Hacd1-fl) isoform during muscle fibre development. (A and B) X-Gal staining of a Hacd1+/− embryo at E12.5 (A), TA muscles (B) from a Hacd1−/− mouse on Day 15 after injection of NaCl (left) or notexin (right). (C) Dissected fibres from the notexin-injected muscle shown in B showing X-Gal staining in a regenerative fibre (centralized nuclei, in blue). Scale bar, 20 μm. (D) RT-PCR experiments showing expression of Hacd1 transcripts in mouse tissues and embryos. (E–H) Expression of Hacd1 transcripts during differentiation of primary muscle cells (E and F) and C2C12 cells (G and H) revealed by RT-PCR experiments (E and G) or RT-qPCR experiments (F and H) showing fold-change from proliferation for each isoform (n = 3 for each condition). (I) RT-qPCR experiments for Hacd1-fl and Hacd1-d5 isoforms in TA muscles from wild-type mice, either non-injected (n = 4) or on Day 6 (n = 3) or Day 15 (n = 4) after notexin injection. Error bars correspond to standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001.

Mentions: During embryogenesis of Hacd1+/− mice, strong expression of the LacZ reporter gene was observed in heart and skeletal muscle precursors (Figure 5A). LacZ expression was also highly induced in adult skeletal muscles during injury-induced regeneration (Figure 5B) and, more precisely, in regenerating myofibres recognizable by the alignment of central nuclei (Figure 5C).Figure 5


HACD1, a regulator of membrane composition and fluidity, promotes myoblast fusion and skeletal muscle growth.

Blondelle J, Ohno Y, Gache V, Guyot S, Storck S, Blanchard-Gutton N, Barthélémy I, Walmsley G, Rahier A, Gadin S, Maurer M, Guillaud L, Prola A, Ferry A, Aubin-Houzelstein G, Demarquoy J, Relaix F, Piercy RJ, Blot S, Kihara A, Tiret L, Pilot-Storck F - J Mol Cell Biol (2015)

Upregulation of the muscle-specific, Hacd1-full length (Hacd1-fl) isoform during muscle fibre development. (A and B) X-Gal staining of a Hacd1+/− embryo at E12.5 (A), TA muscles (B) from a Hacd1−/− mouse on Day 15 after injection of NaCl (left) or notexin (right). (C) Dissected fibres from the notexin-injected muscle shown in B showing X-Gal staining in a regenerative fibre (centralized nuclei, in blue). Scale bar, 20 μm. (D) RT-PCR experiments showing expression of Hacd1 transcripts in mouse tissues and embryos. (E–H) Expression of Hacd1 transcripts during differentiation of primary muscle cells (E and F) and C2C12 cells (G and H) revealed by RT-PCR experiments (E and G) or RT-qPCR experiments (F and H) showing fold-change from proliferation for each isoform (n = 3 for each condition). (I) RT-qPCR experiments for Hacd1-fl and Hacd1-d5 isoforms in TA muscles from wild-type mice, either non-injected (n = 4) or on Day 6 (n = 3) or Day 15 (n = 4) after notexin injection. Error bars correspond to standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4589950&req=5

MJV049F5: Upregulation of the muscle-specific, Hacd1-full length (Hacd1-fl) isoform during muscle fibre development. (A and B) X-Gal staining of a Hacd1+/− embryo at E12.5 (A), TA muscles (B) from a Hacd1−/− mouse on Day 15 after injection of NaCl (left) or notexin (right). (C) Dissected fibres from the notexin-injected muscle shown in B showing X-Gal staining in a regenerative fibre (centralized nuclei, in blue). Scale bar, 20 μm. (D) RT-PCR experiments showing expression of Hacd1 transcripts in mouse tissues and embryos. (E–H) Expression of Hacd1 transcripts during differentiation of primary muscle cells (E and F) and C2C12 cells (G and H) revealed by RT-PCR experiments (E and G) or RT-qPCR experiments (F and H) showing fold-change from proliferation for each isoform (n = 3 for each condition). (I) RT-qPCR experiments for Hacd1-fl and Hacd1-d5 isoforms in TA muscles from wild-type mice, either non-injected (n = 4) or on Day 6 (n = 3) or Day 15 (n = 4) after notexin injection. Error bars correspond to standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001.
Mentions: During embryogenesis of Hacd1+/− mice, strong expression of the LacZ reporter gene was observed in heart and skeletal muscle precursors (Figure 5A). LacZ expression was also highly induced in adult skeletal muscles during injury-induced regeneration (Figure 5B) and, more precisely, in regenerating myofibres recognizable by the alignment of central nuclei (Figure 5C).Figure 5

Bottom Line: We further demonstrate that in normal differentiating myoblasts, expression of the catalytically active HACD1 isoform, which is encoded by a muscle-enriched splice variant, yields decreased lysophosphatidylcholine content, a potent inhibitor of myoblast fusion, and increased concentrations of ≥ C18 and monounsaturated fatty acids of phospholipids.These lipid modifications correlate with a reduction in plasma membrane rigidity.In conclusion, we propose that fusion impairment constitutes a novel, non-exclusive pathological mechanism operating in congenital myopathies and reveal that HACD1 is a key regulator of a lipid-dependent muscle fibre growth mechanism.

View Article: PubMed Central - PubMed

Affiliation: Inserm, IMRB U955-E10, 94000 Créteil, France Université Paris-Est, Ecole nationale vétérinaire d'Alfort (EnvA), 94700 Maisons-Alfort, France Université Paris-Est Créteil, Faculté de médecine, 94000 Créteil, France.

No MeSH data available.


Related in: MedlinePlus