Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20645 (mannose-6-phosphate receptor)
 320 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenocarcinoma of the esophagus develops from metaplastic Barrett's columnar epithelia through the evolution of dysplastic epithelial intermediates. Although the role of dysplasia leading to adenocarcinoma is well established, far less is known regarding the cellular changes involved in this process. Because the development of dysplasia is characterized by the loss of apical secretory specializations, we hypothesized that changes in apical trafficking might be involved in the dysplastic process. We have sought to evaluate the expression of an important candidate regulator of apical trafficking, the small GTP-binding protein, Rab11, in resection and biopsy tissue from patients with Barrett's esophagus. Sections from esophageal resection specimens from 4 patients and endoscopic biopsies from 60 patients were stained with antibodies against Rab11 and Rab25 as well as protein markers of the Golgi apparatus and p53 protein. Rab11 staining in low-grade dysplastic regions was similar to that observed with monoclonal antibodies against Rab25 and gamma-adaptin and colocalized with staining for the Golgi marker, the mannose-6-phosphate receptor. In the esophageal adenocarcinoma resections, prominent Rab11 immunostaining was observed in the supranuclear region of low-grade dysplastic cells. In contrast, regions of high-grade dysplasia demonstrating strong nuclear p53 staining showed only diffuse or absent Rab11 staining. In endoscopic biopsies, 91% of biopsies that were read unanimously as low-grade dysplasia demonstrated supranuclear Rab11 staining. Fourteen percent of biopsies unanimously graded as being without dysplasia demonstrated perinuclear Rab11 staining. No p53 immunostaining was observed in any of the low-grade dysplasia biopsy specimens. An increase in Rab11 immunoreactivity seems to correlate with low-grade dysplasia, whereas p53 immunostaining correlates with high-grade dysplasia. The colocalization of Rab11 staining with increased immunoreactivity for markers of the trans-Golgi system is consistent with a defect in apical trafficking due to an expansion of either the trans-Golgi compartment or the apical recycling vesicle system.
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PMID:Increased immunoreactivity for Rab11, a small GTP-binding protein, in low-grade dysplastic Barrett's epithelia. 938 93

Antigen presentation to CD4(+) T lymphocytes requires transport of newly synthesized major histocompatibility complex (MHC) class II molecules to the endocytic pathway, where peptide loading occurs. This step is mediated by a signal located in the cytoplasmic tail of the MHC class II-associated Ii chain, which directs the MHC class II-Ii complexes from the trans-Golgi network (TGN) to endosomes. The subcellular machinery responsible for the specific targeting of MHC class II molecules to the endocytic pathway, as well as the first compartments these molecules enter after exit from the TGN, remain unclear. We have designed an original experimental approach to selectively analyze this step of MHC class II transport. Newly synthesized MHC class II molecules were caused to accumulate in the Golgi apparatus and TGN by incubating the cells at 19 degrees C, and early endosomes were functionally inactivated by in vivo cross-linking of transferrin (Tf) receptor-containing endosomes using Tf-HRP complexes and the HRP-insoluble substrate diaminobenzidine. Inactivation of Tf-containing endosomes caused a marked delay in Ii chain degradation, peptide loading, and MHC class II transport to the cell surface. Thus, early endosomes appear to be required for delivery of MHC class II molecules to the endocytic pathway. Under cross-linking conditions, most alphabetaIi complexes accumulated in tubules and vesicles devoid of gamma-adaptin and/or mannose-6-phosphate receptor, suggesting an AP1-independent pathway for the delivery of newly synthesized MHC class II molecules from the TGN to endosomes.
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PMID:Early endosomes are required for major histocompatiblity complex class II transport to peptide-loading compartments. 1047 34

The role of ADP-ribosylation factor (Arf) in Golgi associated, gamma-adaptin homologous, Arf-interacting protein (GGA)-mediated membrane traffic was examined. GGA is a clathrin adaptor protein that binds Arf through its GAT domain and the mannose-6-phosphate receptor through its VHS domain. The GAT and VHS domains interacted such that Arf and mannose-6-phosphate receptor binding to GGA were mutually exclusive. In vivo, GGA bound membranes through either Arf or mannose-6-phosphate receptor. However, mannose-6-phosphate receptor excluded Arf from GGA-containing structures outside of the Golgi. These data are inconsistent with predictions based on the model for Arf's role in COPI veside coat function. We propose that Arf recruits GGA to a membrane and then, different from the current model, 'hands-off' GGA to mannose-6-phosphate receptor. GGA and mannose-6-phosphate receptor are then incorporated into a transport intermediate that excludes Arf.
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PMID:Arf regulates interaction of GGA with mannose-6-phosphate receptor. 1253 73

The mammalian acrosome is a secretory vesicle of mature sperms that plays an important role in fertilization. Recent evidence had pointed out that some components found at endosomes in somatic cells are associated with the developing acrosome during the early steps of spermiogenesis. Moreover, the mammalian acrosome contains many enzymes found within lysosomes in somatic cells. In this work, we studied the dynamics of some components of the endosome/lysosome system, as a way to understand the complex membrane trafficking circuit established during spermatogenesis. We show that the cation independent-mannose-6-phosphate receptor (CI-MPR) is transiently expressed in the cytoplasm of mid-stage spermatids (steps 5-11). On the other hand, gamma-adaptin, an adaptor molecule of a complex involved in trafficking from the Golgi to lysosomes, was expressed in cytoplasmic vesicles only in pachytene and Cap-phase spermatids (steps 1-5). Our major finding is that the lysosomal protein LAMP-1 is differentially expressed during spermiogenesis. LAMP-1 appears late in spermatogenesis (Acrosome-phase) contrasting with LAMP-2, which is present throughout the complete process. Both proteins appear to be associated with cytoplasmic vesicles and not with the developing acrosome. None of the studied proteins is present in epididymal spermatozoa. Our results suggest that the CI-MPR could be involved in membrane trafficking and/or acrosomal shaping during spermiogenesis.
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PMID:Differential expression of lysosomal associated membrane protein (LAMP-1) during mammalian spermiogenesis. 1295 Jan 8

A novel peripheral membrane protein (2c18) that interacts directly with the gamma 'ear' domain of the adaptor protein complex 1 (AP-1) in vitro and in vivo is described. Ultrastructural analysis demonstrates a colocalization of 2c18 and gamma1-adaptin at the trans-Golgi network (TGN) and on vesicular profiles. Overexpression of 2c18 increases the fraction of membrane-bound gamma1-adaptin and inhibits its release from membranes in response to brefeldin A. Knockdown of 2c18 reduces the steady-state levels of gamma1-adaptin on membranes. Overexpression or downregulation of 2c18 leads to an increased secretion of the lysosomal hydrolase cathepsin D, which is sorted by the mannose-6-phosphate receptor at the TGN, which itself involves AP-1 function for trafficking between the TGN and endosomes. This suggests that the direct interaction of 2c18 and gamma1-adaptin is crucial for membrane association and thus the function of the AP-1 complex in living cells. We propose to name this protein gamma-BAR.
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PMID:Gamma-BAR, a novel AP-1-interacting protein involved in post-Golgi trafficking. 1577 84