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Document History for Document ID 309224
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| ID:
309224.0,
MPI für molekulare Genetik / Department of Human Molecular Genetics |
| Knockout of Arfrp1 leads to disruption of ARF-like1 (ARL1) targeting to the trans-Golgi in mouse embryos and HeLa cells |
| Authors: | Zahn, Claudia; Hommel, Angela; Lu,, Lei; Hong, Wanjin; Walther, Diego J.; Florian, Simone; Joost, Hans-Georg; Schürmann, Annette | | Language: | English | | Date of Publication (YYYY-MM-DD): | 2006-12-01 | | Title of Journal: | Molecular Membrane Biology | | Journal Abbrev.: | Mol. Membr. Biol. | | Volume: | 23 | | Start Page: | 475 | | End Page: | 485 | | Copyright: | ©2006 Taylor & Francis Group. | | Review Status: | not specified | | Audience: | Experts Only | | Abstract / Description: | ADP-ribosylation factor related protein 1 (ARFRP1) is a member of the ARF-family of GTPases which operate as molecular switches in the regulation of intracellular protein traffic. Deletion of the mouse Arfrp1 gene leads to embryonic lethality during early gastrulation, suggesting that ARFRP1 is required for cell adhesion-related processes. Here we show that ARFRP1 specifically controls targeting of ARL1 and its effector Golgin-245 to the trans-Golgi. GTP-bound ARFRP1 (ARFRP1-Q79L mutant) is associated with Golgi membranes and co-localized with the GTPase ARL1. In contrast, the guanine nucleotide exchange defective ARFRP1 mutant (ARFRP1-T31N) clusters within the cytosol. ARFRP1-T31N or depletion of endogenous ARFRP1 by RNA interference disrupts the Golgi association of ARL1 and of the GRIP-domain protein Golgin-245 and alters the distribution of a trans-Golgi network marker, syntaxin 6. In contrast, the targeting of two other Golgi-associated proteins, GM130 and giantin, was unaffected. Furthermore, in Arfrp1−/ − embryos ARL1 dislocated from Golgi membranes whereas it was associated with intracellular membranes in wild-type embryos. These data suggest that lethality of Arfrp1 knockout embryos is due to a specific disruption of protein targeting, e.g., of ARL1 and Golgin-245, to the Golgi. | | Free Keywords: | ARF-like GTPases, trans-Golgi, embryogenesis, RNA interference | | External Publication Status: | published | | Document Type: | Article |
| Communicated by: | Hans-Hilger Ropers | | Affiliations: | MPI für molekulare Genetik
| | Identifiers: | ISSN:1464-5203
DOI:10.1080/09687860600840100 |
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