scholarly journals SEC18/NSF-independent, protein-sorting pathway from the yeast cortical ER to the plasma membrane

2005 ◽  
Vol 169 (4) ◽  
pp. 613-622 ◽  
Author(s):  
Christoph Jüschke ◽  
Andrea Wächter ◽  
Blanche Schwappach ◽  
Matthias Seedorf
Keyword(s):  
Plasma Membrane ◽  
Membrane Proteins ◽  
Protein Sorting ◽  
Temperature Sensitive ◽  
Cell Periphery ◽  
Yeast Protein ◽  
Local Synthesis ◽  
Sorting Signals ◽  
Necessary And Sufficient ◽  
Independent Protein

Classic studies of temperature-sensitive secretory (sec) mutants have demonstrated that secreted and plasma membrane proteins follow a common SEC pathway via the endoplasmic reticulum (ER), Golgi apparatus, and secretory vesicles to the cell periphery. The yeast protein Ist2p, which is synthesized from a localized mRNA, travels from the ER to the plasma membrane via a novel route that operates independently of the formation of coat protein complex II–coated vesicles. In this study, we show that the COOH-terminal domain of Ist2p is necessary and sufficient to mediate SEC18-independent sorting when it is positioned at the COOH terminus of different integral membrane proteins and exposed to the cytoplasm. This domain functions as a dominant plasma membrane localization determinant that overrides other protein sorting signals. Based on these observations, we suggest a local synthesis of Ist2p at cortical ER sites, from where the protein is sorted by a novel mechanism to the plasma membrane.

scholarly journals Role of the Endocytic Machinery in the Sorting of Lysosome-associated Membrane Proteins

2005 ◽  
Vol 16 (9) ◽  
pp. 4231-4242 ◽  
Author(s):  
Katy Janvier ◽  
Juan S. Bonifacino
Keyword(s):  
Plasma Membrane ◽  
Coat Protein ◽  
Membrane Proteins ◽  
Adaptor Protein ◽  
The Other ◽  
Sorting Signals ◽  
Efficient Delivery ◽  
Endocytic Machinery

The limiting membrane of the lysosome contains a group of transmembrane glycoproteins named lysosome-associated membrane proteins (Lamps). These proteins are targeted to lysosomes by virtue of tyrosine-based sorting signals in their cytosolic tails. Four adaptor protein (AP) complexes, AP-1, AP-2, AP-3, and AP-4, interact with such signals and are therefore candidates for mediating sorting of the Lamps to lysosomes. However, the role of these complexes and of the coat protein, clathrin, in sorting of the Lamps in vivo has either not been addressed or remains controversial. We have used RNA interference to show that AP-2 and clathrin—and to a lesser extent the other AP complexes—are required for efficient delivery of the Lamps to lysosomes. Because AP-2 is exclusively associated with plasma membrane clathrin coats, our observations imply that a significant population of Lamps traffic via the plasma membrane en route to lysosomes.

Recruitment of the endosomal WASH complex is mediated by the extended ‘tail’ of Fam21 binding to the retromer protein Vps35

2012 ◽  
Vol 442 (1) ◽  
pp. 209-220 ◽  
Author(s):  
Michael E. Harbour ◽  
Sophia Y. Breusegem ◽  
Matthew N. J. Seaman
Keyword(s):  
Membrane Proteins ◽  
Protein Sorting ◽  
Complex Interaction ◽  
Membrane Association ◽  
Tail Domain ◽  
Fk506 Binding Protein ◽  
Retromer Complex ◽  
Multimeric Protein ◽  
Vacuolar Protein ◽  
Necessary And Sufficient

The retromer complex is a conserved endosomal protein sorting complex that sorts membrane proteins into nascent endosomal tubules. The recognition of membrane proteins is mediated by the cargo-selective retromer complex, a stable trimer of the Vps35 (vacuolar protein sorting 35), Vps29 and Vps26 proteins. We have recently reported that the cargo-selective retromer complex associates with the WASH (Wiskott–Aldrich syndrome homologue) complex, a multimeric protein complex that regulates tubule dynamics at endosomes. In the present study, we show that the retromer–WASH complex interaction occurs through the long unstructured ‘tail’ domain of the WASH complex–Fam21 protein binding to Vps35, an interaction that is necessary and sufficient to target the WASH complex to endosomes. The Fam21-tail also binds to FKBP15 (FK506-binding protein 15), a protein associated with ulcerative colitis, to mediate the membrane association of FKBP15. Elevated Fam21-tail expression inhibits the association of the WASH complex with retromer, resulting in increased cytoplasmic WASH complex. Additionally, overexpression of the Fam21-tail results in cell-spreading defects, implicating the activity of the WASH complex in regulating the mobilization of membrane into the endosome-to-cell surface pathway.

scholarly journals Role of N-glycosylation in trafficking of apical membrane proteins in epithelia

2009 ◽  
Vol 296 (3) ◽  
pp. F459-F469 ◽  
Author(s):  
Olga Vagin ◽  
Jeffrey A. Kraut ◽  
George Sachs
Keyword(s):  
Plasma Membrane ◽  
Membrane Proteins ◽  
Membrane Transporters ◽  
Membrane Domains ◽  
Sorting Signals ◽  
Galectin 3 ◽  
Vectorial Functions ◽  
Apical Sorting ◽  
Golgi Network

Polarized distribution of plasma membrane transporters and receptors in epithelia is essential for vectorial functions of epithelia. This polarity is maintained by sorting of membrane proteins into apical or basolateral transport containers in the trans-Golgi network and/or endosomes followed by their delivery to the appropriate plasma membrane domains. Sorting depends on the recognition of sorting signals in proteins by specific sorting machinery. In the present review, we summarize experimental evidence for and against the hypothesis that N-glycans attached to the membrane proteins can act as apical sorting signals. Furthermore, we discuss the roles of N-glycans in the apical sorting event per se and their contribution to folding and quality control of glycoproteins in the endoplasmic reticulum or retention of glycoproteins in the plasma membrane. Finally, we review existing hypotheses on the mechanism of apical sorting and discuss the potential roles of the lectins, VIP36 and galectin-3, as putative apical sorting receptors.

Aberrant Protein Sorting to the Nucleus during Erythroblast Enucleation: Mechanistic Basis for Membrane Protein Loss in Hereditary Elliptocytosis and Spherocytosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1559-1559
Author(s):  
Marcela A. Salomao ◽  
Sarah Short ◽  
Gloria Lee ◽  
Xiuli An ◽  
Mohandas Narla ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Membrane Proteins ◽  
Plasma Membranes ◽  
Molecular Mechanisms ◽  
Protein Sorting ◽  
Transmembrane Proteins ◽  
Hereditary Elliptocytosis ◽  
Skeletal Protein ◽  
Aberrant Protein ◽  
Protein 4.1R

Abstract During erythroblast enucleation, nuclei surrounded by plasma membrane separate from erythroblast cytoplasm. A key aspect of this process is sorting of membrane components to plasma membranes surrounding expelled nuclei and young reticulocytes. This protein partitioning performs a crucial role in regulating the protein content of reticulocyte plasma membranes. Although it is known that cytoskeletal actin, spectrin and protein 4.1R distribute to reticulocytes, little is known about the sorting patterns of erythroblast transmembrane proteins. In hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), erythrocytes contain well-described deficiencies of various transmembrane proteins, in addition to those encoded by the mutant genes. For example, elliptocytic human and murine erythrocytes resulting from mutations in the 4.1R gene lack not only protein 4.1R but also transmembrane protein glycophorin C (GPC), known to be a 4.1R binding partner with a key role in linking cytoskeleton to bilayer. Similarly, in HS resulting from mutations in the ankyrin gene, deficiencies of band 3, Rh and GPA have been documented. Various molecular mechanisms could explain deficiencies of membrane proteins in HS and HE erythrocytes including: perturbed trafficking to the erythroblast membrane; aberrant protein sorting during erythroblast enucleation; and selective loss during reticulocyte membrane remodeling. We explored whether aberrant protein sorting during enucleation might be responsible for GPC deficiency in HE. First we performed immunochemical analysis of the sorting pattern of GPC using highly purified extruded nuclei and immature reticulocytes derived from terminally differentiated murine erythroblast cultures. Proteins from equivalent numbers of expelled nuclei and reticulocytes were analyzed by Western blotting. Using antibodies specific for GPC we determined that 90% of GPC sorted to reticulocyte plasma membranes. To validate these results we used live cell, three-color immunofluorescent microscopy and analyzed enucleating erythroblasts, reticulocytes and extruded nuclei from freshly harvested murine wild type bone marrow. Independently confirming the Western blot data, we found that GPC sorted almost exclusively to reticulocytes with little or no GPC in association with nuclear plasma membrane. Strikingly, in 4.1R null erythroblasts GPC was distributed exclusively to expelled nuclei. These findings unequivocally establish that skeletal protein 4.1R is critical for normal sorting of GPC to young reticulocytes and provide clear evidence that specific skeletal protein associations can regulate protein sorting during enucleation. Moreover, our data provide a molecular explanation for the underlying basis of GPC deficiency observed in 4.1R-deficient individuals with HE. We speculate that aberrant protein sorting may be a prevalent mechanism for the deficiencies of various membrane proteins in HS and HE and that their differential loss could contribute to the variable phenotypic expression of these hemolytic disorders.

scholarly journals Segregation in the Golgi complex precedes export of endolysosomal proteins in distinct transport carriers

2017 ◽  
Vol 216 (12) ◽  
pp. 4141-4151 ◽  
Author(s):  
Yu Chen ◽  
David C. Gershlick ◽  
Sang Yoon Park ◽  
Juan S. Bonifacino
Keyword(s):  
Plasma Membrane ◽  
Membrane Proteins ◽  
Golgi Complex ◽  
Adaptor Proteins ◽  
Transmembrane Domains ◽  
The Other ◽  
Present Evidence ◽  
Sorting Signals ◽  
Vesicular Carriers ◽  
Classical Models

Biosynthetic sorting of newly synthesized transmembrane cargos to endosomes and lysosomes is thought to occur at the TGN through recognition of sorting signals in the cytosolic tails of the cargos by adaptor proteins, leading to cargo packaging into coated vesicles destined for the endolysosomal system. Here we present evidence for a different mechanism in which two sets of endolysosomal proteins undergo early segregation to distinct domains of the Golgi complex by virtue of the proteins’ luminal and transmembrane domains. Proteins in one Golgi domain exit into predominantly vesicular carriers by interaction of sorting signals with adaptor proteins, but proteins in the other domain exit into predominantly tubular carriers shared with plasma membrane proteins, independently of signal–adaptor interactions. These findings demonstrate that sorting of endolysosomal proteins begins at an earlier stage and involves mechanisms that partly differ from those described by classical models.

scholarly journals An Endosome-to-Plasma Membrane Pathway Involved in Trafficking of a Mutant Plasma Membrane ATPase in Yeast

2000 ◽  
Vol 11 (2) ◽  
pp. 579-592 ◽  
Author(s):  
Wen-jie Luo ◽  
Amy Chang
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Secretory Pathway ◽  
Protein Sorting ◽  
Temperature Sensitive ◽  
Plasma Membrane Atpase ◽  
Vacuolar Protein Sorting ◽  
Membrane Atpase ◽  
Vacuolar Protein ◽  
Endosomal System

The plasma membrane ATPase, encoded by PMA1, is delivered to the cell surface via the secretory pathway. Previously, we characterized a temperature-sensitive pma1 mutant in which newly synthesized Pma1-7 is not delivered to the plasma membrane but is mislocalized instead to the vacuole at 37°C. Severalvps mutants, which are defective in vacuolar protein sorting, suppress targeting-defective pma1 by allowing mutant Pma1 to move once again to the plasma membrane. In this study, we have analyzed trafficking in the endosomal system by monitoring the movement of Pma1-7 in vps36, vps1, andvps8 mutants. Upon induction of expression, mutant Pma1 accumulates in the prevacuolar compartment in vps36cells. After chase, a fraction of newly synthesized Pma1-7 is delivered to the plasma membrane. In both vps1 andvps8 cells, newly synthesized mutant Pma1 appears in small punctate structures before arrival at the cell surface. Nevertheless, biosynthetic membrane traffic appears to follow different routes in vps8 and vps1: the vacuolar protein-sorting receptor Vps10p is stable in vps8 but not in vps1. Furthermore, a defect in endocytic delivery to the vacuole was revealed in vps8 (andvps36) but not vps1 by endocytosis of the bulk membrane marker FM 4-64. Moreover, in vps8 cells, there is defective down-regulation from the cell surface of the mating receptor Ste3, consistent with persistent receptor recycling from an endosomal compartment to the plasma membrane. These data support a model in which mutant Pma1 is diverted from the Golgi to the surface invps1 cells. We hypothesize that in vps8and vps36, in contrast to vps1, mutant Pma1 moves to the surface via endosomal intermediates, implicating an endosome-to-surface traffic pathway.

SEC-independent protein sorting to the yeast plasma membrane

2007 ◽  
Vol 2007 (Spring) ◽  
Author(s):  
Kiran Maass ◽  
Marcel Fischer ◽  
Ebru Ercan ◽  
Teshager Bitew ◽  
Matthias Seedorf
Keyword(s):  
Plasma Membrane ◽  
Protein Sorting ◽  
Yeast Plasma Membrane ◽  
Independent Protein
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