AlphaS1-casein deficiency due to defective genotypes induces a chronic ER stress and deep changes in milk composition, signing a singular secretion mode in goats - Archive ouverte HAL Accéder directement au contenu
Communication Dans Un Congrès Année : 2012

AlphaS1-casein deficiency due to defective genotypes induces a chronic ER stress and deep changes in milk composition, signing a singular secretion mode in goats

Résumé

The extensive polymorphism recorded at the CSN1S1 locus was shown to influence goat milk composition and its technological properties. A deficit in alphaS1-casein is responsible for the accumulation of immature caseins in distended rough endoplasmic reticulum (ER) cisternae of mammary epithelial cells (MEC). This triggers a chronic ER stress which in turn induces an adaptive unfolded protein response (UPR). Our data strongly suggest that alphaS1-casein interacts with the other caseins as from the ER and that this complex is required for their transport to the Golgi. A differential proteomic analysis (2D-DIGE) of milks from goats of extreme genotypes (A/A vs. O/O) at the CSN1S1 locus revealed the over representation of ER-resident proteins in O/O milks, strongly suggesting a singular secretion mechanism for this genotype. In addition, goats of A/A genotype produce fat globules larger in size and displaying significant differences in MFGM composition, including both MFGM proteins and polar lipids. The effects of the genotype at the CSN1S1 locus on the profiles of oligosaccharides (OS), which are also built within the ER where both lipids and caseins are synthesized, have been investigated. The milk free OS were profiled and their structures elucidated. A relationship between genotypes at the CSN1S1 locus and milk OS expression was observed, demonstrating the influence of genotypes on OS structure and composition. Finally, using different functional genomic approaches, we succeeded in highlighting the general dysfunction occurring in MEC from alphaS1-casein deficient animals, and in identifying genes contributing to the adaptive UPR and proteins involved in the transport between the ER and the Golgi apparatus, as well as enzymes participating to the biosynthesis of lipid droplets, the precursors of MFGs. Taken together our results demonstrate that a close mechanistic relationship exists between biosynthesis and secretion pathways of the main components of milk: casein micelles, milk fat globules and oligosaccharides. We definitely demonstrated the relevance of the goat model as an experimental system to unravel the underlying mechanisms and to appraise the possibility to dissociate these biosynthesis pathways in order to modulate selectively one or the other. A large part of this work was funded by ANR (Genanimal program) and APIS Gène.

Domaines

Autre [q-bio.OT]
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Dates et versions

hal-01019037 , version 1 (07-07-2014)

Identifiants

  • HAL Id : hal-01019037 , version 1
  • PRODINRA : 172579

Citer

Patrice Martin, Bouabid Badaoui, D. Barile, Hichem Lahouassa, Christian Beauvallet, et al.. AlphaS1-casein deficiency due to defective genotypes induces a chronic ER stress and deep changes in milk composition, signing a singular secretion mode in goats. 11. International Conference on Goats, International Goat Association (IGA). USA., Sep 2012, Gran Canaria, Spain. pp.65. ⟨hal-01019037⟩
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