| Dileucine signal-dependent and AP-1-independent targeting of a lysosomal glycoprotein in Trypanosoma brucei. | |
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MedLine Citation:
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PMID: 17869353 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Sorting of trans-membrane proteins destined for the lysosome is achieved by selective inclusion into post-Golgi transport vesicles. In higher eukaryotes sorting may be mediated by a peptidic motif, principally acidic clusters and tyrosine- or dileucine-based cytoplasmic signals or by inclusion of mannose-6-phosphate (M6P) into the N-glycans of lysosomal proteins. In African trypanosomes a major lysosomal trans-membrane protein is CB-1/p67. The cytoplasmic domain of p67 lacks tyrosine and lysine, but does contain a canonical dileucine sequence embedded within an acidic region. AP-1, -3 and -4 adaptin complexes, which recognise tyrosine- and dileucine-sorting signals, are encoded by the trypanosome genome, but the genes for M6P-receptors or activities required to produce M6P are absent, suggesting that lysosomal delivery of p67 is most likely adaptin-mediated. By construction of p67 reporter constructs we show that the dileucine signal is necessary and sufficient for efficient lysosomal delivery of a trans-membrane protein in bloodstream stage trypanosomes. However, this targeting does not require AP-1, as knockdown of the trypanosome gamma-adaptin subunit by RNAi has no detectable effect on the location or maturation of p67. These data suggest that p67 is targeted to the lysosome by dileucine-dependent but AP-1-independent mechanisms. |
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Authors:
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Clare L Allen; Dangjin Liao; Wei-Lian Chung; Mark C Field |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-08-06 |
Journal Detail:
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Title: Molecular and biochemical parasitology Volume: 156 ISSN: 0166-6851 ISO Abbreviation: Mol. Biochem. Parasitol. Publication Date: 2007 Dec |
Date Detail:
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Created Date: 2007-10-29 Completed Date: 2008-02-26 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8006324 Medline TA: Mol Biochem Parasitol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 175-90 Citation Subset: IM |
Affiliation:
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The Molteno Building, Department of Pathology, Tennis Court Road, University of Cambridge, Cambridge CB2 1QP, UK. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Motifs Animals Artificial Gene Fusion Genes, Reporter Glycoproteins / chemistry, genetics, metabolism* Lysosomes / metabolism* Protein Sorting Signals / genetics*, physiology* Protein Transport Protozoan Proteins / chemistry, genetics, metabolism Trypanosoma brucei brucei / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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//Wellcome Trust |
| Chemical | |
Reg. No./Substance:
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0/Glycoproteins; 0/Protein Sorting Signals; 0/Protozoan Proteins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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