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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.

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Related in: MedlinePlus

HACD1 regulates lipid balance and membrane fluidity in myoblasts. (A) Lysophosphatidylcholine (LPC) content, expressed as the percentage of total phospholipids, in proliferation and on Day 3 of differentiation. (B) Ratio of C18-26 to C10-16 phospholipid fatty acids in proliferation and on Day 3 of differentiation. (C) Proportions of saturated (SFA), monounsaturated (MUFA), or polyunsaturated (PUFA) fatty acids on Day 3 of differentiation. (D) Fluorescence anisotropy (r, inverse of fluidity) measured on Day 3 of differentiation. (E) Proposed model for the role of Hacd1-fl during muscle fibre development. Error bars correspond to standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001.
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MJV049F7: HACD1 regulates lipid balance and membrane fluidity in myoblasts. (A) Lysophosphatidylcholine (LPC) content, expressed as the percentage of total phospholipids, in proliferation and on Day 3 of differentiation. (B) Ratio of C18-26 to C10-16 phospholipid fatty acids in proliferation and on Day 3 of differentiation. (C) Proportions of saturated (SFA), monounsaturated (MUFA), or polyunsaturated (PUFA) fatty acids on Day 3 of differentiation. (D) Fluorescence anisotropy (r, inverse of fluidity) measured on Day 3 of differentiation. (E) Proposed model for the role of Hacd1-fl during muscle fibre development. Error bars correspond to standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001.

Mentions: As lysophosphatidylcholine (LPC) acts as a potent inhibitor of myoblast fusion when added to the differentiation medium (Leikina et al., 2013), we first evaluated whether the relative content of phospholipid species would be modified upon Hacd1 modulation (Supplementary Table S2). In control myoblasts, differentiation was accompanied by a nearly two-fold drop in LPC that was abolished in sh-Hacd1 myoblasts and fully restored in sh-Hacd1+FL cells (Figure 7A and Supplementary Table S2A). This global dynamic profile was underlain by the individual profile of most LPCs (Supplementary Table S2B). This result demonstrated that HACD1-FL activity is responsible for the drop in LPC content preceding fusion. Myoblast differentiation was also accompanied by an increase in the level of phosphatidylinositols and a decrease in lysophosphatidylethanolamines that were independent of Hacd1 expression (Supplementary Table S2A).Figure 7


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)

HACD1 regulates lipid balance and membrane fluidity in myoblasts. (A) Lysophosphatidylcholine (LPC) content, expressed as the percentage of total phospholipids, in proliferation and on Day 3 of differentiation. (B) Ratio of C18-26 to C10-16 phospholipid fatty acids in proliferation and on Day 3 of differentiation. (C) Proportions of saturated (SFA), monounsaturated (MUFA), or polyunsaturated (PUFA) fatty acids on Day 3 of differentiation. (D) Fluorescence anisotropy (r, inverse of fluidity) measured on Day 3 of differentiation. (E) Proposed model for the role of Hacd1-fl during muscle fibre development. 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

License
Show All Figures
getmorefigures.php?uid=PMC4589950&req=5

MJV049F7: HACD1 regulates lipid balance and membrane fluidity in myoblasts. (A) Lysophosphatidylcholine (LPC) content, expressed as the percentage of total phospholipids, in proliferation and on Day 3 of differentiation. (B) Ratio of C18-26 to C10-16 phospholipid fatty acids in proliferation and on Day 3 of differentiation. (C) Proportions of saturated (SFA), monounsaturated (MUFA), or polyunsaturated (PUFA) fatty acids on Day 3 of differentiation. (D) Fluorescence anisotropy (r, inverse of fluidity) measured on Day 3 of differentiation. (E) Proposed model for the role of Hacd1-fl during muscle fibre development. Error bars correspond to standard error of the mean. *P < 0.05, **P < 0.01, ***P < 0.001.
Mentions: As lysophosphatidylcholine (LPC) acts as a potent inhibitor of myoblast fusion when added to the differentiation medium (Leikina et al., 2013), we first evaluated whether the relative content of phospholipid species would be modified upon Hacd1 modulation (Supplementary Table S2). In control myoblasts, differentiation was accompanied by a nearly two-fold drop in LPC that was abolished in sh-Hacd1 myoblasts and fully restored in sh-Hacd1+FL cells (Figure 7A and Supplementary Table S2A). This global dynamic profile was underlain by the individual profile of most LPCs (Supplementary Table S2B). This result demonstrated that HACD1-FL activity is responsible for the drop in LPC content preceding fusion. Myoblast differentiation was also accompanied by an increase in the level of phosphatidylinositols and a decrease in lysophosphatidylethanolamines that were independent of Hacd1 expression (Supplementary Table S2A).Figure 7

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