Document Detail

Exposed thiols confer localization in the endoplasmic reticulum by retention rather than retrieval.
MedLine Citation:
PMID:  8824258     Owner:  NLM     Status:  MEDLINE    
The cysteine present in the Ig micro chain tailpiece (microtp) prevents the secretion of unpolymerized IgM intermediates and causes their accumulation in the endoplasmic reticulum (ER). In principle, this can be the consequence of actual retention in this organelle or of retrieval from the Golgi. To determine which of the two mechanisms underlies the cysteine-dependent ER localization, we analyze here the post-translational modifications of suitably engineered cathepsin D (CD) molecules. The glycans of this protease are phosphorylated by post-ER phosphotransferases and further modified in the trans-Golgi to generate a mannose 6-phosphate lysosome targeting signal. Only trace amounts of the mutp-tagged CD (CDM&mutpCys) are phosphorylated, unless retention is reversed by exogenous reducing agents or the critical cysteine mutated (CDMmutpSer). In contrast, a KDEL-tagged CD, that is retrieved from the Golgi into the ER, acquires phosphates, though mainly resistant to alkaline phosphatase. Similarly to CDMmutpSer, the few CDMmutpCys molecules that escape retention and acquire phosphates in the cis-Golgi are transported beyond the KDEL retrieval compartment, as indicated by their sensitivity to alkaline phosphatase. These results demonstrate that the thiol-dependent ER localization arises primarily from true retention, without recycling through the Golgi.
C Isidoro; C Maggioni; M Demoz; A Pizzagalli; A M Fra; R Sitia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  271     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1996 Oct 
Date Detail:
Created Date:  1996-11-26     Completed Date:  1996-11-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  26138-42     Citation Subset:  IM    
Dipartimento di Medicina ed Oncologia Sperimentale, Sez. di Patologia Generale, Università di Torino, 10125 Torino, Italy.
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MeSH Terms
Biological Transport
COS Cells
Cathepsin D / genetics,  metabolism*
Endoplasmic Reticulum / metabolism*
Immunoglobulin M / metabolism
Microscopy, Fluorescence
Models, Biological
Oligopeptides / metabolism*
Phosphates / metabolism
Plasmids / metabolism
Protein Sorting Signals*
Recombinant Fusion Proteins / metabolism
Subcellular Fractions / metabolism
Sulfhydryl Compounds / metabolism*
Reg. No./Substance:
0/Immunoglobulin M; 0/Oligopeptides; 0/Phosphates; 0/Protein Sorting Signals; 0/Recombinant Fusion Proteins; 0/Sulfhydryl Compounds; 113516-56-6/lysyl-aspartyl-glutamyl-leucine; EC D

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