scholarly journals CROP: A Retromer-PROPPIN complex mediating membrane fission in the endo-lysosomal system

2021 ◽  
Author(s):  
Andreas Mayer ◽  
Courtellement Thibault ◽  
Maria Giovanna De Leo ◽  
Navin Gopaldass
Keyword(s):  
Plasma Membrane ◽  
Membrane Receptors ◽  
Strong Preference ◽  
The Novel ◽  
Membrane Fission ◽  
Lysosomal System ◽  
Endosomal Transport ◽  
Plasma Membrane Receptors ◽  
And Control

Endo-lysosomal compartments exchange proteins by fusing, fissioning, and through endosomal transport carriers. Thereby, they sort many plasma membrane receptors and transporters and control cellular signaling and metabolism. How the membrane fission events are catalyzed is poorly understood. Here, we identify the novel CROP complex as a factor acting at this step. CROP joins members of two protein families: the peripheral subunits of retromer, a coat forming endosomal transport carriers, and membrane inserting PROPPINs. Integration into CROP potentiates the membrane fission activity of the PROPPIN Atg18 on synthetic liposomes and confers strong preference for binding PI(3,5)P2, a phosphoinositide required for membrane fission activity. Disrupting CROP blocks fragmentation of lysosome-like yeast vacuoles in vivo. CROP-deficient mammalian endosomes accumulate micrometer-long tubules and fail to export cargo, suggesting that carriers attempt to form but cannot separate from these organelles. PROPPINs compete for retromer binding with the SNX proteins, which recruit retromer to the membrane during the formation of endosomal carriers. Transition from retromer-SNX complexes to retromer-PROPPIN complexes might hence switch retromer activities from cargo capture to membrane fission.

Down-regulation in vivo of PGE receptors and adenylate cyclase stimulation

1980 ◽  
Vol 239 (1) ◽  
pp. E75-E80
Author(s):  
R. P. Robertson ◽  
K. R. Westcott ◽  
D. R. Storm ◽  
M. G. Rice
Keyword(s):  
Plasma Membrane ◽  
Adenylate Cyclase ◽  
Binding Affinity ◽  
Membrane Receptors ◽  
Cyclase Activity ◽  
Adenylate Cyclase Activity ◽  
Down Regulation ◽  
Liver Plasma Membrane ◽  
Plasma Membrane Receptors

Down-regulation in vivo of liver plasma membrane receptors for prostaglandin E (PGE) was investigated in Sprague-Dawley rats using the 16,16-dimethyl analogue of PGE2, This analogue was used for subcutaneous injections because it escapes the rapid pulmonic degradation characteristic of PGE and was recognized well by liver plasma membrane receptors. Following treatment with the analogue, the concentration of PGE receptors was significantly decreased (-37%, P less than 0.001), but the binding affinity was not altered. There was no evidence for carry-through of the analogue into the isolated plasma membrane preparation. It was also demonstrated that GTP decreased the binding affinity between PGE and its receptor. Down-regulation of receptor concentration was associated with a significant decrease (P less than 0.001) in PGE1-stimulated plasma membrane adenylate cyclase activity. These data provide the novel demonstration that rat liver plasma membrane receptor for PGE can be down-regulated in vivo and that this causes a corresponding decrease in PGE-induced plasma membrane adenylate cyclase activity.

scholarly journals Plasma membrane glycosphingolipid signaling: a turning point

2021 ◽  
Author(s):  
Elena Chiricozzi
Keyword(s):  
Plasma Membrane ◽  
Chemical Synthesis ◽  
Bioinformatic Analysis ◽  
Membrane Receptors ◽  
Outer Side ◽  
Neuronal Homeostasis ◽  
Extracellular Stimuli ◽  
Conceptual Shift ◽  
Plasma Membrane Receptors ◽  
Key Events

AbstractPlasma membrane interaction is highly recognized as an essential step to start the intracellular events in response to extracellular stimuli. The ways in which these interactions take place are less clear and detailed. Over the last decade my research has focused on developing the understanding of the glycosphingolipids-protein interaction that occurs at cell surface. By using chemical synthesis and biochemical approaches we have characterized some fundamental interactions that are key events both in the immune response and in the maintenance of neuronal homeostasis. In particular, for the first time it has been demonstrated that a glycolipid, present on the outer side of the membrane, the long-chain lactosylceramide, is able to directly modulate a cytosolic protein. But the real conceptual change was the demonstration that the GM1 oligosaccharide chain is able, alone, to replicate numerous functions of GM1 ganglioside and to directly interact with plasma membrane receptors by activating specific cellular signaling. In this conceptual shift, the development and application of multidisciplinary techniques in the field of biochemistry, from chemical synthesis to bioinformatic analysis, as well as discussions with several national and international colleagues have played a key role.

scholarly journals Effects of cytoplasmic acidification on clathrin lattice morphology.

1989 ◽  
Vol 108 (2) ◽  
pp. 401-411 ◽  
Author(s):  
J Heuser
Keyword(s):  
Plasma Membrane ◽  
Cultured Cells ◽  
Membrane Receptors ◽  
The Other ◽  
Culture Dish ◽  
Initial Curvature ◽  
Internal Ph ◽  
Cytoplasmic Acidification

Reducing the internal pH of cultured cells by several different protocols that block endocytosis is found to alter the structure of clathrin lattices on the inside of the plasma membrane. Lattices curve inward until they become almost spherical yet remain stubbornly attached to the membrane. Also, the lattices bloom empty "microcages" of clathrin around their edges. Correspondingly, broken-open cells bathed in acidified media demonstrate similar changes in clathrin lattices. Acidification accentuates the normal tendency of lattices to round up in vitro and also stimulates them to nucleate microcage formation from pure solutions of clathrin. On the other hand, several conditions that also inhibit endocytosis have been found to create, instead of unusually curved clathrin lattices with extraneous microcages, a preponderance of unusually flat lattices. These treatments include pH-"clamping" cells at neutrality with nigericin, swelling cells with hypotonic media, and sticking cells to the surface of a culture dish with soluble polylysine. Again, the unusually flat lattices in such cells display a tendency to round up and to nucleate clathrin microcage formation during subsequent in vitro acidification. This indicates that regardless of the initial curvature of clathrin lattices, they all display an ability to grow and increase their curvature in vitro, and this is enhanced by lowering ambient pH. Possibly, clathrin lattice growth and curvature in vivo may also be stimulated by a local drop in pH around clusters of membrane receptors.

Developmentally regulated expression of insulin-like growth factors by differentiated murine teratocarcinomas and extraembryonic mesoderm

Development ◽  
1986 ◽  
Vol 95 (1) ◽  
pp. 193-212
Author(s):  
John K. Heath ◽  
Wai-Kang Shi
Keyword(s):  
Plasma Membrane ◽  
Binding Protein ◽  
Membrane Receptors ◽  
Developmentally Regulated ◽  
Igf Receptors ◽  
Igf Binding ◽  
Plasma Membrane Receptors ◽  
Igf Binding Protein ◽  
Culture Supernatants ◽  
Insulin Like Growth Factors

The expression of plasma membrane receptors for insulin-like growth factors (IGFs) by PC13 embryonal carcinoma (EC) cells, and their immediate differentiated progeny PC13END was examined by binding radiolabelled IGF-I to cell monolayers. Both cell types express high-affinity IGF receptors, but the apparent number of unoccupied receptor sites falls by about 60% upon differentiation. Crosslinking studies reveal that both type 1 and type 2 IGF receptors are expressed by PC13EC cells. PC13END-cell-conditioned medium contains developmentally regulated, separable activities, one of which reacts directly with IGF-II, and the other with IGF for plasma membrane receptors. The former activity represents a soluble secreted IGF-binding protein. The latter activity is structurally and functionally similar to rat IGF-II. Polyclonal antibodies raised against purified rat IGF-II specifically recognize multiple forms of IGF in radiolabelled culture supernatants and material which closely resembles the soluble IGF-binding protein. Immunoprecipitation of radiolabelled culture supernatants with anti-rat IGF-II reveals that the differentiation of PC13EC cells is accompanied by the coexpression of IGF-like molecules and the soluble binding protein, and that IGF-like molecules are expressed by extraembryonic tissues of mesodermal origin in the early postimplantation mouse embryo. These findings show that IGF-like molecules are expressed in early mammalian development and may act in an autocrine fashion in vivo.

scholarly journals Murine fetal liver macrophages bind developing erythroblasts by a divalent cation-dependent hemagglutinin.

1988 ◽  
Vol 106 (3) ◽  
pp. 649-656 ◽  
Author(s):  
L Morris ◽  
P R Crocker ◽  
S Gordon
Keyword(s):  
Plasma Membrane ◽  
Divalent Cation ◽  
Plasma Membranes ◽  
Fetal Liver ◽  
Divalent Cations ◽  
Membrane Receptors ◽  
Erythroid Cells ◽  
Mammalian Development ◽  
Trypsin Treatment ◽  
Plasma Membrane Receptors

During mammalian development the fetal liver plays an important role in hematopoiesis. Studies with the macrophage (M phi)-specific mAb F4/80 have revealed an extensive network of M phi plasma membranes interspersed between developing erythroid cells in fetal liver. To investigate the interactions between erythroid cells and stromal M phi, we isolated hematopoietic cell clusters from embryonic day-14 murine fetal liver by collagenase digestion and adherence. Clusters of erythroid cells adhered to glass mainly via M phi, 94% of which bound 19 +/- 11 erythroblasts (Eb) per cell. Bound Eb proliferated vigorously on the surface of fetal liver M phi, with little evidence of ingestion. The M phi could be stripped of their associated Eb and the clusters then reconstituted by incubation with Eb in the presence of divalent cations. The interaction required less Ca++ than Mg++, 100 vs. 250 microM for half-maximal binding, and was mediated by a trypsin-sensitive hemagglutinin on the M phi surface. After trypsin treatment fetal liver M phi recovered the ability to bind Eb and this process could be selectively inhibited by cycloheximide. Inhibition tests showed that the Eb receptor differs from known M phi plasma membrane receptors and fetal liver M phi did not bind sheep erythrocytes, a ligand for a distinct M phi hemagglutinin. We propose that fetal liver M phi interact with developing erythroid cells by a novel nonphagocytic surface hemagglutinin which is specific for a ligand found on Eb and not on mature red cells.

scholarly journals Internalization of lectins in neuronal GERL.

1977 ◽  
Vol 73 (1) ◽  
pp. 1-13 ◽  
Author(s):  
N K Gonatas ◽  
S U Kim ◽  
A Stieber ◽  
S Avrameas
Keyword(s):  
Plasma Membrane ◽  
Membrane Receptors ◽  
Dorsal Root Ganglion Neurons ◽  
Cytochemical Study ◽  
Receptor Complexes ◽  
Mouse Dorsal Root Ganglion ◽  
Respiration Inhibitors ◽  
Ricin Agglutinin ◽  
Plasma Membrane Receptors ◽  
Ganglion Neurons

Conjugates of ricin agglutinin and phytohemagglutinin with horseradish peroxidase (HRP) were used for a cytochemical study of internalization of their plasma membrane "receptors" in cultured isolated mouse dorsal root ganglion neurons. Labeling of cells with lectin-HRP was done at 4 degrees C, and internalization was performed at 37 degrees C in a culture medium free of lectin-HRP. 15-20 min after incubation at 37 degrees C, lectin-HRP receptor complexes were seen in vesicles or tubules located near the plasma membrane. After 1-3 h at 37 degrees C, lectin-HRP-receptor complexes accumulated in vesicles and tubules corresponding to acid phosphatase-rich vesicles and tubules (GERL) at the trans aspect of the Golgi apparatus. A few coated vesicles and probably some dense bodies contained HRP after 3-6 h of incubation at 37 degrees C. Soluble HRP was not endocytosed under the conditions of this experiment or when it was present in the incubation medium at 37 degrees C. Internalization of lectin-HRP-receptor conjugates was decreased or inhibited by mitochondrial respiration inhibitors but not by cytochalasin B or colchicine. These studies indicate that lectin-labeled plasma membrane moieties of neurons are endocytosed primarily in elements of GERL.

Sign in / Sign up

Export Citation Format

Share Document