Identification of a putative effector protein for rab11 that participates in transferrin recycling Journal Article
| Authors: | Zeng, J.; Ren, M.; Gravotta, D.; De Lemos-Chiarandini, C.; Lui, M.; Erdjument-Bromage, H.; Tempst, P.; Xu, G.; Shen, T. H.; Morimoto, T.; Adesnik, M.; Sabatini, D. D. |
| Article Title: | Identification of a putative effector protein for rab11 that participates in transferrin recycling |
| Abstract: | We have identified and cloned the cDNA for a 912-aa protein, rab11BP, that interacts with the GTP-containing active form of rab11, a GTP-binding protein that plays a critical role in receptor recycling. Although rab11BP is primarily cytosolic, a significant fraction colocalizes with rab11 in endosomal membranes of both the sorting and recycling subcompartments. In vitro binding of rab11 to native rab11BP requires partial denaturation of the latter to expose an internal binding site located between residues 334 and 504 that is apparently masked by the C-terminal portion of the protein, which includes six repeats known as WD40 domains. Within the cell, rab11BP must undergo a conformational change in which the rab11-binding site becomes exposed, because when coexpressed with rab11 in transfected cells the two proteins formed abundant complexes in association with membranes. Furthermore, although overexpression of rab11BP did not affect transferrin recycling, overexpression of a truncated form of the protein, rab11BP(1- 504), that includes the rab11-binding site but lacks the WD40 domains inhibited recycling as strongly as does a dominant negative rab11 mutant protein that does not bind GTP. Strikingly, the inhibition caused by the truncated rab11BP was prevented completely when the cells also expressed a C- terminally deleted, nonprenylatable form of rab11 that, by itself, has no effect on recycling. We propose that rab11BP is an effector for rab11, whose association with this GTP-binding protein is dependent on the action of another membrane-associated factor that promotes the unmasking of the rab11- binding site in rab11BP. |
| Keywords: | unclassified drug; nonhuman; conference paper; protein conformation; protein localization; animal cell; mouse; animals; mice; protein protein interaction; gtp-binding proteins; gene expression regulation; molecular cloning; cloning, molecular; amino acid sequence; molecular sequence data; protein purification; dog; nucleotide sequence; conformational transition; guanosine triphosphate; guanine nucleotide binding protein; complementary dna; 3t3 cells; transferrin; dna, complementary; receptor protein; protein denaturation; rab protein; rab gtp-binding proteins; humans; priority journal; protein rab11 |
| Journal Title: | Proceedings of the National Academy of Sciences of the United States of America |
| Volume: | 96 |
| Issue: | 6 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Date Published: | 1999-03-16 |
| Start Page: | 2840 |
| End Page: | 2845 |
| Language: | English |
| DOI: | 10.1073/pnas.96.6.2840 |
| PUBMED: | 10077598 |
| PROVIDER: | scopus |
| PMCID: | PMC15856 |
| DOI/URL: | |
| Notes: | Conference Paper -- Export Date: 16 August 2016 -- Source: Scopus |
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