The Role of N-Glycosylation in Transport to the Plasma Membrane and Sorting of the Neuronal Glycine Transporter GLYT2

Maza, Rodrigo M.; Poyatos, Irene; López-Corcuera, Beatriz; Núñez, Enrique; Giménez, Cecilio; Zafra, Francisco; Aragón, Carmen

doi:10.1074/jbc.m006774200

Cited by 96 publications

(81 citation statements)

References 51 publications

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“…Similarly, Scheiffele et al (26) have shown that a growth hormone, HG, which is a non-glycosylated protein secreted equally from the apical and basolateral domains of the plasma membrane, is secreted preferentially from apical membrane when an N-glycosylation site is introduced by mutagenesis. Furthermore, glycine transporter GLYT2, which localizes in the apical surface in polarized MDCK cells, was distributed in a nonpolarized manner by unglycosylation (27).…”

Section: Discussionmentioning

confidence: 99%

Involvement of VIP36 in Intracellular Transport and Secretion of Glycoproteins in Polarized Madin-Darby Canine Kidney (MDCK) Cells

Hara-Kuge

Ohkura

Ideo

et al. 2002

Journal of Biological Chemistry

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VIP36, an intracellular lectin that recognizes high mannose-type glycans (Hara-Kuge, S., Ohkura, T., Seko, A., and Yamashita, K. (1999) Glycobiology 9, 833-839), was shown to localize not only to the early secretory pathway but also to the plasma membrane of MadinDarby canine kidney (MDCK) cells. In the plasma membrane, VIP36 exhibited an apical-predominant distribution, the apical/basolateral ratio being ϳ2. Like VIP36, plasma membrane glycoproteins recognized by VIP36 were found in the apical and basolateral membranes in the ratio of ϳ2 to 1. In addition, secretory glycoproteins recognized by VIP36 were secreted ϳ2-fold more efficiently from the apical membrane than from the basolateral membrane. Thus, the apical/basolateral ratio of the transport of VIP36-recognized glycoproteins was correlated with that of VIP36 in MDCK cells. Upon overproduction of VIP36 in MDCK cells, the apical/basolateral ratios of both VIP36 and VIP36-recognized glycoproteins were changed from ϳ2 to ϳ4, and the secretion of VIP36-recognized glycoproteins was greatly stimulated. In contrast to the overproduction of VIP36, that of a mutant version of VIP36, which has no lectin activity, was of no effect on the distribution of glycoproteins to apical and basolateral membranes and inhibited the secretion of VIP36-recognized glycoproteins. Furthermore, the overproduction of VIP36 greatly stimulated the secretion of a major apical secretory glycoprotein of MDCK cells, clusterin, which was found to carry at least one high mannose-type glycan and to be recognized by VIP36. In contrast to the secretion of clusterin, that of a non-glycosylated apical-secretion protein, galectin-3, was not stimulated through the overproduction of VIP36. These results indicated that VIP36 was involved in the transport and sorting of glycoproteins carrying high mannose-type glycan(s).Newly synthesized secretory and membrane proteins exit from the ER 1 in transport vesicles targeted to the Golgi apparatus. Vesicular transport through the Golgi is often accompanied by post-translational modifications, such as glycosylation of cargo proteins until they have reached the trans-Golgi Network. In the trans-Golgi Network, proteins are sorted into vesicles bound for different destinations including the plasma membrane, the endosome/lysosome, and secretory granules. The protein sorting has been one of the most interesting issues in the study of vesicular protein traffic processes, but its molecular mechanisms remain largely unresolved.It has been recently demonstrated that intracellular lectins play important roles in vesicular transport: for example, mannose-6-phosphate receptor (1) as a receptor recognizing the marker for lysosomal enzymes, calnexin (2, 3) and calreticulin (4) as molecular chaperones, and ERGIC-53 (5) possibly as a transport cargo receptor. ERGIC-53 is an intermediate compartment marker (6), and it is identical to MR60, a mannosespecific membrane lectin (7) with a carbohydrate-binding domain homologous to that of lectins of leguminous plants (8). The N-term...

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Section: Discussionmentioning

confidence: 99%

Involvement of VIP36 in Intracellular Transport and Secretion of Glycoproteins in Polarized Madin-Darby Canine Kidney (MDCK) Cells

Hara-Kuge

Ohkura

Ideo

et al. 2002

Journal of Biological Chemistry

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“…However, when we inhibited O-glycosylation, CX 3 CL1 still trafficked to the apical membrane. For other proteins, such as endolyn and the glycine transporter GLYT2, N-glycosylation is the crucial determinant of apical targeting (49,50). CX 3 CL1 has a single N-glycosylation site, located in the chemokine domain (2).…”

Section: Discussionmentioning

confidence: 99%

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

Durkan¹,

Alexander²,

Liu³

et al. 2007

Journal of the American Society of Nephrology

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The chemokine CX 3 CL1 plays a key role in glomerulonephritis and can act as both chemoattractant and adhesion molecule. CX 3 CL1 also is upregulated in tubulointerstitial injury, but little is known about the subcellular distribution and function of CX 3 CL1 in renal tubular epithelial cells (RTEC). Unexpectedly, it was found that CX 3 CL1 is expressed predominantly on the apical surface of tubular epithelium in human renal transplant biopsy specimens with acute rejection or acute tubular necrosis. For studying the targeting of CX 3 CL1 in polarized RTEC, MDCK cells that expressed untagged or green fluorescent protein-tagged CX 3 CL1 were generated. The chemokine was present on the apical membrane and in subapical vesicles. Apical targeting of CX 3 CL1 was not due to signals that were conferred by its intracellular domain, to associations with lipid rafts, or to O-glycosylation but, rather, depended on N-linked glycosylation of the protein. With the use of fluorescence recovery after photobleaching, it was found that CX 3 CL1 is immobile in the apical membrane. However, CX 3 CL1 partitioned with the triton-soluble rather than -insoluble cellular fraction, indicating that it is not associated directly with the actin cytoskeleton or with lipid rafts. Accordingly, disruption of rafts through cholesterol depletion did not render CX 3 CL1 mobile. For exploration of potential functions of apical CX 3 CL1, binding of CX 3 CR1-expressing leukocytes to polarized RTEC was examined. Leukocyte adhesion to the luminal surface was enhanced significantly when CX 3 CL1 was present. These data demonstrate that CX 3 CL1 is expressed preferentially on the apical membrane of RTEC and suggest a novel function for the chemokine in recruitment and retention of leukocytes in tubulointerstitial inflammation.

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“…As the vesicular transporter VGAT/VIAAT is nonselective for GABA or glycine (which compete for it; Chaudhry et al 1998;Wojcik et al 2006), such a scenario would imply diVerential sorting and/ or membrane availability of membrane transporters for glycine and GABA. Indeed, there is a growing body of evidence that points to an intricate regulation of the sorting and membrane insertion of Glyt2, Gat-1, and Gat-2 (e.g., Muth et al 1998;Martinez-Maza et al 2001;Farhan et al 2008; see also Chiu et al 2002), which are expressed in large molecular layer interneurons of the cerebellum (cf the Allen Brain Atlas; Lein et al 2007). Intriguingly, Gat-2 is subject to regulation by serotonin; as mentioned above, Lugaro cells are the primary target of serotoninergic projections to the cerebellar cortex (Dieudonne and Dumoulin 2000).…”

Section: Large Inhibitory Interneurons Of the Granule Cell Layermentioning

confidence: 99%

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

Schilling

Oberdick

Rossi

et al. 2008

Histochem Cell Biol

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Ever since the groundbreaking work of Ramon y Cajal, the cerebellar cortex has been recognized as one of the most regularly structured and wired parts of the brain formed by a rather limited set of distinct cells. Its rather protracted course of development, which persists well into postnatal life, the availability of multiple natural mutants, and, more recently, the availability of distinct molecular genetic tools to identify and manipulate discrete cell types have suggested the cerebellar cortex as an excellent model to understand the formation and working of the central nervous system. However, the formulation of a unifying model of cerebellar function has so far proven to be a most cantankerous problem, not least because our understanding of the internal cerebellar cortical circuitry is clearly spotty. Recent research has highlighted the fact that cerebellar cortical interneurons are a quite more diverse and heterogeneous class of cells than generally appreciated, and have provided novel insights into the mechanisms that underpin the development and histogenetic integration of these cells. Here, we provide a short overview of cerebellar cortical interneuron diversity, and we summarize some recent results that are hoped to provide a primer on current understanding of cerebellar biology.

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The Role of N-Glycosylation in Transport to the Plasma Membrane and Sorting of the Neuronal Glycine Transporter GLYT2

Cited by 96 publications

References 51 publications

Involvement of VIP36 in Intracellular Transport and Secretion of Glycoproteins in Polarized Madin-Darby Canine Kidney (MDCK) Cells

Involvement of VIP36 in Intracellular Transport and Secretion of Glycoproteins in Polarized Madin-Darby Canine Kidney (MDCK) Cells

Expression and Targeting of CX3CL1 (Fractalkine) in Renal Tubular Epithelial Cells

Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

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