Control of membrane protein homeostasis by a chaperone-like glial cell adhesion molecule at multiple subcellular locations

The significance of crosstalks among constituents of plasma membrane protein clusters/complexes in cellular proteostasis and protein quality control (PQC) remains incompletely understood. Examining the glial (enriched) cell adhesion molecule (CAM), we demonstrate its chaperone-like role in the biosynthetic processing of the megalencephalic leukoencephalopathy with subcortical cyst 1 (MLC1)-heteromeric regulatory membrane protein complex, as well as the function of the GlialCAM/MLC1 signalling complex. We show that in the absence of GlialCAM, newly synthesized MLC1 molecules remain unfolded and are susceptible to polyubiquitination-dependent proteasomal degradation at the endoplasmic reticulum. At the plasma membrane, GlialCAM regulates the diffusional partitioning and endocytic dynamics of cluster members, including the ClC-2 chloride channel and MLC1. Impaired folding and/or expression of GlialCAM or MLC1 in the presence of diseases causing mutations, as well as plasma membrane tethering compromise the functional expression of the cluster, leading to compromised endo-lysosomal organellar identity. In addition, the enlarged endo-lysosomal compartments display accelerated acidification, ubiquitinated cargo-sorting and impaired endosomal recycling. Jointly, these observations indicate an essential and previously unrecognized role for CAM, where GliaCAM functions as a PQC factor for the MLC1 signalling complex biogenesis and possess a permissive role in the membrane dynamic and cargo sorting functions with implications in modulations of receptor signalling.

ПРИНЦИП ВОЗМОЖНЫХ ПЕРЕМЕЩЕНИЙ В МОМЕНТНОМЕМБРАННОЙ ДИНАМИЧЕСКОЙ ТЕОРИИ УПРУГИХ ТОНКИХ ОБОЛОЧЕК / The Principle of Possible Displacments in the Moment-Membrane Dynamic Theory of Elastic Thin Shells

В работе излагается моментно-мембранная динамическая теория упругих тонких оболочек на основе метода гипотез, который соответствует качественной стороне результата интегрирования трехмерной граничной задачи моментной теории упругости в тонкой области оболочки. На основе принципа возможных перемещений трехмерной моментной динамической теории упругости с независимыми полями перемещений и вращений и основных соотношений моментномембранной динамической теории упругих тонких оболочек, устанавливается принцип возможных перемещений для моментномембранной динамической теории упругих тонких оболочек./ In the present paper the moment-membrane dynamic theory of elastic thin shells is presented based on the hypotheses method, which corresponds to the qualitative side of the result of integration of the three-dimensional boundary-value problem of the moment theory of elasticity in a thin region of the shell. On the basis of the principle of possible displacements of the threedimensional moment dynamic theory of elasticity with independent fields of displacements and rotations and the basic relations of the moment-membrane dynamic theory of elastic thin shells, the principle of possible displacements for the moment-membrane dynamic theory of elastic thin shells is established.

Effect of 17β-estradiol on a Human Vaginal Lactobacillus Crispatus Strain

Lactobacillis and estrogens are essential in vaginal homeostasis. In the present study, we investigated the potential direct effect of 17β-estradiol on a vaginal strain of Lactobacillus cristapus, the major bacterial species of the vaginal microbiota. 17β-estradiol (10− 6 to 10− 10 M) has no effect on the growth of L. crispatus but markedly affects its membrane dynamic. This effect appears adaptative and coherent with a signal transduction process. The surface polarity and aggregation potential of the bacteria remains unchanged after exposure to 17β-estradiol but its mean size is significantly reduced. 17β-estradiol also promotes biosurfactant production by L. crispatus and adhesion to vaginal VK2/E6E7 cells. Conversely, the biofilm formation activity of the bacterium is marginally affected. A potential 17β-estradiol binding site was identified by bioinformatics in L. crispatus as the membrane lipid rafts associated SPFH domain containing protein. Taken together, this study reveals that 17β-estradiol can exert direct effects on L. crispatus. This process might be of importance in the vaginal environment physiology by promoting adhesion of Lactobacilli to the mucosa and providing protection against pathogens.

Exploring the trans-membrane dynamic mechanisms of single polyamidoamine nano-drugs via a “force tracing” technique

Considerable success has been achieved in the drug delivery of nano-drugs for chemotherapy, but the main obstacles in understanding the drug delivery dynamic mechanisms for nano-drug applications stem from technical limitations.

Novel negatively-charged membrane adsorbers made using combination of photopolymerization and immersion precipitation

A novel method combining a traditional immersion precipitation process for making membranes with photopolymerization and crosslinking of functional monomers included in the casting solution was used to prepare asymmetric polyethersulfone membranes with submicron particles incorporating glycidyl methacrylate copolymer. In order to introduce sulfonic groups epoxide rings of glycidyl methacrylate were opened using two methods. The first method was functionalization with sodium sulfite, and the second method was functionalization with sulfuric acid and then grafting with 2-acrylamido-2-methylpropane sulfonic acid. Obtained membranes were characterized using infrared spectroscopy, conductometric titration and water permeability measurements. Scanning electron microscopy and atomic force microscopy were used to investigate the surface morphology and topology of membrane. Dynamic adsorption of Rhodamine B as a model dye was used to demonstrate suitability of these novel membranes for membrane adsorption since the adsorption capacity for dye cations was much better for both functionalized membrane with sodium sulfite and grafted membrane with 2-acrylamido-2-methylpropane sulfonic acid compared to the nonfunctionalized membrane.