Characteristics and Structural Requirements of Apical Sorting of the Rat Growth Hormone through the O-Glycosylated Stalk Region of Intestinal Sucrase-isomaltase

Spodsberg, Nikolaj; Alfalah, Marwan; Naim, Hassan Y.

doi:10.1074/jbc.m108187200

Cited by 20 publications

(14 citation statements)

References 47 publications

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“…This stalk region was also required for apical secretion of a truncated form of p75, suggesting that a membrane tether is not required for recognition of the sorting information in this portion of the protein. Similarly, the appendage of an O-glycosylated stalk, important for apical sorting of sucrase-isomaltase to the secreted protein rGH, caused the chimera to be secreted predominantly into the apical medium (Alfalah et al, 1999;Spodsberg et al, 2001). In this case, O-glycosylation led to the association of rGH with detergent-resistant microdomains, as also observed for sucraseisomaltase.…”

Section: Carbohydrates As Apical Sorting Determinantsmentioning

confidence: 75%

Apical trafficking in epithelial cells: signals, clusters and motors

Weisz

Rodríguez-Boulan

2009

Journal of Cell Science

284

281

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In the early days of epithelial cell biology, researchers working with kidney and/or intestinal epithelial cell lines and with hepatocytes described the biosynthetic and recycling routes followed by apical and basolateral plasma membrane (PM) proteins. They identified the trans-Golgi network and recycling endosomes as the compartments that carried out apical-basolateral sorting. They described complex apical sorting signals that promoted association with lipid rafts, and simpler basolateral sorting signals resembling clathrin-coated-pit endocytic motifs. They also noticed that different epithelial cell types routed their apical PM proteins very differently, using either a vectorial (direct) route or a transcytotic (indirect) route. Although these original observations have generally held up, recent studies have revealed interesting complexities in the routes taken by apically destined proteins and have extended our understanding of the machinery required to sustain these elaborate sorting pathways. Here, we critically review the current status of apical trafficking mechanisms and discuss a model in which clustering is required to recruit apical trafficking machineries. Uncovering the mechanisms responsible for polarized trafficking and their epithelial-specific variations will help understand how epithelial functional diversity is generated and the pathogenesis of many human diseases.

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Section: Carbohydrates As Apical Sorting Determinantsmentioning

confidence: 75%

Apical trafficking in epithelial cells: signals, clusters and motors

Weisz

Rodríguez-Boulan

2009

Journal of Cell Science

284

281

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“…The apical targeting of a transmembrane protein in MDCK cells can be mediated by a variety of signals, including glycosylation motifs and amino acid sequences located within the extracellular, transmembrane, or intracellular domain (18,35,63,64). Both N-and O-glycans are postulated to mediate apical targeting in a number or proteins (35,36,65,66) via incorporation into lipid rafts via putative raft-associated carbohydrate-binding lectins localized to the TGN (20,67). However, there are examples where apical targeting may depend on glycosylation, yet be independent of raft The apical targeting determinants of the M 2 receptor were able to override the basolateral sorting information contained in the M 4 receptor.…”

Section: Discussionmentioning

confidence: 99%

Identification of a Novel Apical Sorting Motif and Mechanism of Targeting of the M2 Muscarinic Acetylcholine Receptor

Chmelar¹,

Nathanson²

2006

Journal of Biological Chemistry

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Previous studies have shown that the M 2 receptor is localized at steady state to the apical domain in Madin-Darby canine kidney (MDCK) epithelial cells. In this study, we identify the molecular determinants governing the localization and the route of apical delivery of the M 2 receptor. First, by confocal analysis of a transiently transfected glycosylation mutant in which the three putative glycosylation sites were mutated, we determined that N-glycans are not necessary for the apical targeting of the M 2 receptor. Next, using a chimeric receptor strategy, we found that two independent sequences within the M

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“…The latter usually confer localization to the apical membrane (Brown et al, 1989;Lisanti et al, 1989), but alone are not always sufficient (Brown and London, 1998;Benting et al, 1999a). Both N-and O-glycosylation of the extracellular domain have been implicated in apical targeting (Scheiffele et al, 1995;Yeaman et al, 1997;Gut et al, 1998;Spodsberg et al, 2001). Finally, oligomerization of membrane proteins may be an important sorting determinant, particularly for apical transport.…”

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confidence: 99%

Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane

Schuck

Simons

2004

Journal of Cell Science

293

253

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5955Polarized cells establish and maintain functionally distinct surface domains by an elaborate sorting process, which ensures accurate delivery of biosynthetic cargo to different parts of the plasma membrane. This is particularly evident in polarized epithelial cells, which have been used as a model system for studies of sorting mechanisms. The clustering of lipid rafts through the oligomerization of raft components could be utilized for segregating apical from basolateral cargo and for the generation of intracellular transport carriers. Besides functioning in polarized sorting in differentiated cells, raft clustering might also play an important role in the biogenesis of apical membrane domains during development. Mechanisms of polarized sorting A polarized surface distribution of proteins and lipids can be achieved by targeted delivery or selective retention (Yeaman et al., 1999;Matter, 2000). Targeted delivery relies on the segregation of cargo molecules destined for different plasma membrane domains before they reach the cell surface. Selective retention works by trapping them once they arrivefor instance, by anchoring to a domain-specific cytoskeletal scaffold. Proteins delivered to the wrong surface domain are removed by endocytosis and are then degraded or undergo another round of delivery. Targeted delivery and selective retention can be combined such that selective retention enhances the accuracy of intracellular sorting (Mays et al., 1995).The basolateral as well as the apical sorting pathway has been suspected to involve bulk flow, but it is now clear that neither is a general default pathway for the surface delivery of proteins. Instead, apical and basolateral sorting are both governed by sorting determinants embedded in cargo proteins. Sorting determinantsSorting determinants in membrane proteins can reside in the cytoplasmic domain, membrane anchor or extracellular domain (Table 1). Cytoplasmic domain determinants include the basolateral-targeting, tyrosine-based and dileucine motifs (Matter and Mellman, 1994), PDZ-domain-binding motifs and a growing list of unrelated sequences (Altschuler et al., 2003;Muth and Caplan, 2003). Determinants in membrane anchors include the transmembrane domains of some apically targeted viral proteins (Kundu et al., 1996; Lin et al., 1998) and glycosylphosphatidylinositol (GPI) anchors. The latter usually confer localization to the apical membrane (Brown et al., 1989;Lisanti et al., 1989), but alone are not always sufficient (Brown and London, 1998;Benting et al., 1999a). Both N-and O-glycosylation of the extracellular domain have been implicated in apical targeting (Scheiffele et al., 1995;Yeaman et al., 1997;Gut et al., 1998;Spodsberg et al., 2001). Finally, oligomerization of membrane proteins may be an important sorting determinant, particularly for apical transport. Evidence in epithelial cells is lacking so far, but sorting of the voltagegated potassium channel Kv1 into the axonal pathway of neurons, which is related to the apical pathway of epithelial cells ...

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Characteristics and Structural Requirements of Apical Sorting of the Rat Growth Hormone through the O-Glycosylated Stalk Region of Intestinal Sucrase-isomaltase

Cited by 20 publications

References 47 publications

Apical trafficking in epithelial cells: signals, clusters and motors

Apical trafficking in epithelial cells: signals, clusters and motors

Identification of a Novel Apical Sorting Motif and Mechanism of Targeting of the M2 Muscarinic Acetylcholine Receptor

Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane

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