Unconventional secretion of α-Crystallin B requires the Autophagic pathway and is controlled by phosphorylation of its serine 59 residue

α-Crystallin B (CRYAB or HspB5) is a chaperone member of the small heat-shock protein family that prevents aggregation of many cytosolic client proteins by means of its ATP-independent holdase activity. Surprisingly, several reports show that CRYAB exerts a protective role also extracellularly, and it has been recently demonstrated that CRYAB is secreted from human retinal pigment epithelial cells by an unconventional secretion pathway that involves multi-vesicular bodies. Here we show that autophagy is crucial for this unconventional secretion pathway and that phosphorylation at serine 59 residue regulates CRYAB secretion by inhibiting its recruitment to the autophagosomes. In addition, we found that autophagosomes containing CRYAB are not able to fuse with lysosomes. Therefore, CRYAB is capable to highjack and divert autophagosomes toward the exocytic pathway, inhibiting their canonical route leading to the lysosomal compartment. Potential implications of these findings in the context of disease-associated mutant proteins turn-over are discussed

Influence of ewe feeding systems on carcass quality of suckling lambs

Numerous studies have evidenced significant differences in the carcass and meat quality of grass-fed and concentrate-fed lambs. The main differences regard carcass fatness (Murphy et al., 1994), subcutaneous fat colour (Prache and Theriez, 1999), meat colour (Priolo et al., 2002a) and fatty acid composition (Enser et al., 1998). The use of grazing in lamb feeding favours the presence of substances in the meat which are beneficial to human health. Different methods, based on the spectrophotometric properties of fat have been proposed to verify the origin of the product (Priolo et al., 2002b). The objective of the present study is to verify if and to what extent the carcass quality of suckling lambs is affected by ewe feeding systems

Fatty acid profile in the ruminal fluid and in the m. longissimus dorsi of lambs fed herbage or concentrate with or without tannins

Twenty-eight male lambs were divided into two groups at age 45 d. Fourteen lambs were given fresh herbage (vetch); the remaining lambs were fed a concentrate-based diet. Within each treatment, seven lambs received a supplementation of quebracho tannins. At slaughter (age 105 d) the ruminal content and the muscle longissimus dorsi (LD) were collected. Ruminal fluid and LD fatty acid composition was determined by gas chromatography. Among the concentrates-fed lambs, tannins supplementation reduced (P < 0.05) the concentration of C18:0 (- 49 %) and increased vaccenic acid (VA; + 69 %) in the ruminal fluid. When tannins were included into the concentrate, the LD contained double levels of rumenic acid (RA) as compared to the LD of the lambs fed the tannins-free concentrate (0.96 vs. 0.46 % of total extracted fatty acids, respectively; P < 0.05). The concentration of PUFA was higher (P < 0.05) and SFA (P < 0.01) lower in the LD from lambs fed the tannin diets as compared to the animals receiving the tannin-free diets. In conclusion, tannins reduce the biohydrogenation of the PUFA in the rumen. This implies that tannins supplementation could be a strategy to increase the RA and PUFA content and to reduce the SFA into ruminant meats

Influence of ewe feeding systems on meat quality of suckling lambs

In recent years interest has grown in the zootechnical exploitation of environmental feeding resources, above all in marginal areas. The survival of these areas is linked to the development of the limited available resources. Of these, natural pastures represent one of the most important, not only because their zootechnical utilisation permits savings in alimentary costs, but above all because it results in better quality dairy and meat products. The aim of this study is to verify if and to what level ewe feeding systems influence the meat quality of suckling lambs

Early onset effects of single substrate accumulation recapitulate major features of LSD in patient-derived lysosomes.

Lysosome functions mainly rely on their ability to either degrade substrates or release them into the extracellular space. Lysosomal storage disorders (LSDs) are commonly characterized by a chronic lysosomal accumulation of different substrates, thereby causing lysosomal dysfunctions and secretion defects. However, the early effects of substrate accumulation on lysosomal homeostasis have not been analyzed so far. Here, we describe how the acute accumulation of a single substrate determines a rapid centripetal redistribution of the lysosomes, triggering their expansion and reducing their secretion, by limiting the motility of these organelles toward the plasma membrane. Moreover, we provide evidence that such defects could be explained by a trapping mechanism exerted by the extensive contacts between the enlarged lysosomes and the highly intertwined membrane structures of the endoplasmic reticulum which might represent a crucial biological cue ultimately leading to the clinically relevant secondary defects observed in the LSD experimental models and patients