Arfophilins are dual Arf/Rab 11 binding proteins that regulate recycling endosome distribution and are related to Drosophila nuclear fallout

Hickson, Gilles R. X. and Matheson, Johanne and Riggs, Blake and Maier, Valerie H. and Fielding, Andrew B. and Prekeris, Rytis and Sullivan, William and Barr, Francis A. and Gould, Gwyn W. (2003) Arfophilins are dual Arf/Rab 11 binding proteins that regulate recycling endosome distribution and are related to Drosophila nuclear fallout. Molecular Biology of the Cell, 14 (7). pp. 2908-2920. ISSN 1059-1524

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Abstract

Arfophilin is an ADP ribosylation factor (Arf) binding protein of unknown function. It is identical to the Rab11 binding protein eferin/Rab11-FIP3, and we show it binds both Arf5 and Rab11. We describe a related protein, arfophilin-2, that interacts with Arf5 in a nucleotide-dependent manner, but not Arf1, 4, or 6 and also binds Rab11. Arfophilin-2 localized to a perinuclear compartment, the centrosomal area, and focal adhesions. The localization of arfophilin-2 to the perinuclear compartment was selectively blocked by overexpression of Arf5-T31N. In contrast, a green fluorescent protein-arfophilin-2 chimera or arfophilin-2 deletions were localized around the centrosome in a region that was also enriched for transferrin receptors and Rab11 but not early endosome markers, suggesting that the distribution of the endosomal recycling compartment was altered. The arfophilins belong to a conserved family that includes Drosophila melanogaster nuclear fallout, a centrosomal protein required for cellularization. Expression of green fluorescent protein-nuclear fallout in HeLa cells resulted in a similar phenotype, indicative of functional homology and thus implicating the arfophilins in mitosis/cytokinesis. We suggest that the novel dual GTPase-binding capacity of the arfophilins could serve as an interface of signals from Rab and Arf GTPases to regulate membrane traffic and integrate distinct signals in the late endosomal recycling compartment.

Item Type: Journal Article
Journal or Publication Title: Molecular Biology of the Cell
Uncontrolled Keywords: /dk/atira/pure/subjectarea/asjc/1300/1312
Subjects:
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 124299
Deposited By: ep_importer_pure
Deposited On: 28 Mar 2018 12:24
Refereed?: Yes
Published?: Published
Last Modified: 22 Jun 2019 08:27
URI: https://eprints.lancs.ac.uk/id/eprint/124299

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