Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Residence of luminal ER proteins is mediated by a cyclic process which involves binding of escaped proteins to a KDEL receptor in a post-ER compartment and redistribution of the ligand-receptor complex back to the ER. We examined the relocation of the KDEL receptor after treatment with the fungal metabolite brefeldin A and compared this with the retrograde transport of the KDEL receptor observed after ligand or receptor overexpression. Incubation with brefeldin A led to the formation of vesicular structures containing the KDEL receptor and ERGIC-53, a marker for the ER-Golgi intermediate compartment. Immunoelectron microscopy revealed that these structures are composed of tubulo-vesicular clusters. The brefeldin A induced vesicular structures were morphologically and biochemically distinct from the ER-Golgi hybrid compartment as demonstrated by double immunofluorescence microscopy and subcellular fractionation. Overexpression of the receptor itself or a lysozyme-KDEL construct led to a shift of the KDEL receptor together with ERGIC-53, an intermediate compartment marker to the ER but not to structures resembling BFA induced vesicular structures. Moreover, overexpression of the receptor resulted in the partial redistribution of marker proteins of the medial Golgi and the trans-Golgi network to ER-like structures. We conclude that the effects of brefeldin A on the redistribution of the KDEL receptor do not reflect physiological events occurring during increased occupancy of the receptor with ligands.
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PMID:Characterization of brefeldin A induced vesicular structures containing cycling proteins of the intermediate compartment/cis-Golgi network. 907 41

To investigate the role of the KDEL receptor in the retrieval of protein toxins to the mammalian cell endoplasmic reticulum (ER), lysozyme variants containing AARL or KDEL C-terminal tags, or the human KDEL receptor, have been expressed in toxin-treated COS 7 and HeLa cells. Expression of the lysozyme variants and the KDEL receptor was confirmed by immunofluorescence. When such cells were challenged with diphtheria toxin (DT) or Escherichia coli Shiga-like toxin 1 (SLT-1), there was no observable difference in their sensitivities as compared to cells which did not express these exogenous proteins. By contrast, the cytotoxicity of Pseudomonas exotoxin A (PE) is reduced by expressing lysozyme-KDEL, which causes a redistribution of the KDEL receptor from the Golgi complex to the ER, and cells are sensitised to this toxin when they express additional KDEL receptors. These data suggest that, in contrast to SLT-1, PE can exploit the KDEL receptor in order to reach the ER lumen where it is believed that membrane transfer to the cytosol occurs. This contention was confirmed by microinjecting into Vero cells antibodies raised against the cytoplasmically exposed tail of the KDEL receptor. Immunofluorescence confirmed that these antibodies prevented the retrograde transport of the KDEL receptor from the Golgi complex to the ER, and this in turn reduced the cytotoxicity of PE, but not that of SLT-1, to these cells.
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PMID:The KDEL retrieval system is exploited by Pseudomonas exotoxin A, but not by Shiga-like toxin-1, during retrograde transport from the Golgi complex to the endoplasmic reticulum. 991 59