AlphaS1-casein deficiency recorded for defective genotypes induces a chronic ER stress and deep changes in milk composition, signing a singular secretion process in goats

• Main Authors: Martin, Patrice, Badaoui, B, Barile, Daniela, Lahouassa, Hichem, Beauvallet, Christian, Cebo, Christelle, Leroux, Christine, Chanat, Eric
• Other Authors: Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Foods for Health Institute, University of California Davis (UC Davis), University of California-University of California, Unité Mixte de Recherche sur les Herbivores - UMR 1213 (UMRH), Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Unité de recherche génomique et physiologie de la lactation (GPL), Institut National de la Recherche Agronomique (INRA)
• Format: Conference Object
• Language: English
• Published: HAL CCSD 2013
• Subjects: [SDV]Life Sciences [q-bio]; Norway; Tromsø
• Online Access: https://hal.archives-ouvertes.fr/hal-01193994; https://hal.archives-ouvertes.fr/hal-01193994/document; https://hal.archives-ouvertes.fr/hal-01193994/file/13Martin32_1.pdf

The extensive polymorphism recorded at the CSN1S1 locus has been 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 induces, in turn, an adaptive unfolded protein response (UPR). Our data strongly suggest: i) the existence of a membraneassociated form of alphaS1-casein, which is required for efficient export of the other caseins from the ER to the Golgi apparatus; ii) that alphaS1-casein plays a key role in the early steps of casein micelle biogenesis. 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 O/O genotype produce fat globules smaller in size and displaying significant differences in MFGM composition, including both MFGM proteins and polar lipids. A relationship between genotypes at the CSN1S1 locus and the profile (structure and composition) of milk free oligosaccharides (OS), which are also built within the ER, has been shown, thus providing additional evidence for the impact of alphaS1-casein deficiency on the functioning of MEC.