The PX-BAR membrane-remodeling unit of sorting nexin 9

Sorting nexins (SNXs) form a family of proteins known to interact with components in the endosomal system and to regulate various steps of vesicle transport. Sorting nexin 9 (SNX9) is involved in the late stages of clathrin-mediated endocytosis in non-neuronal cells, where together with the GTPase dynamin, it participates in the formation and scission of the vesicle neck. We report here crystal structures of the functional membrane-remodeling unit of SNX9 and show that it efficiently tubulates lipid membranes in vivo and in vitro. Elucidation of the protein superdomain structure, together with mutational analysis and biochemical and cell biological experiments, demonstrated how the SNX9 PX and BAR domains work in concert in targeting and tubulation of phosphoinositide-containing membranes. The study provides insights into the SNX9-induced membrane modulation mechanism

Maternal supply of methionine during late-pregnancy enhances rate of Holstein calf development in utero and postnatal growth to a greater extent than colostrum source

BackgroundPregnancy and early life are critical periods of plasticity during which the fetus and neonate may be influenced by environmental factors such as nutrition. Maternal methionine (Met) supply in non-ruminants during pregnancy can affect offspring development and growth. Thus, the objective of this study was to investigate if increasing Met supply during late-pregnancy affects developmental parameters of the calf at birth and if either maternal Met or colostrum from Met-fed cows alters calf growth. Calves born to Holstein cows individually-fed a basal control [CON; 1.47 Mcal/kg dry matter (DM) and 15.3% crude protein] diet with no added Met or CON plus ethylcellulose rumen-protected Met (MET; Mepron (R) at 0.09% of diet DM; Evonik Nutrition & Care GmbH, Germany) during the last 282 d of pregnancy were used. A total of 39 calves were in CON (n=22 bulls, 17 heifers) and 42 in MET (n=20 bulls, 22 heifers). At birth, calves were randomly allocated considering dam treatment and colostrum as follows: 1) calves from CON cows and colostrum from CON cows (n=21); 2) calves from CON cows and colostrum from MET cows (n=18); 3) calves from MET cows and colostrum from MET cows (n=22); and 4) calves from MET cows and colostrum from CON cows (n=20). All calves were housed, managed, and fed individually during the first 9 wk of life.ResultsDespite greater daily DM intake pre-partum in cows fed MET (15.7 vs. 14.4 +/- 0.12kg/d, P0.05) due to maternal Met supply or colostrum source. However, fecal scores tended to be lower (P0.10) in MET calves regardless of colostrum source.Conclusions Increasing the maternal supply of MET during late-pregnancy enhanced growth in utero as well as during the pre-weaning and early post-weaning periods. Although the similar to 1kg/d greater DM intake during the last 2-3 wk prior to parturition could explain a portion of the 2kg extra body mass of MET calves at birth, other mechanisms potentially encompassing nutrient assimilation efficiency likely played a role. Assessing the exact mechanisms sensitive to supply of Met or total amino acid supply during the latter stages of growth in utero merit further research