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  Knockout of Arfrp1 leads to disruption of ARF-like1 (ARL1) targeting to the trans-Golgi in mouse embryos and HeLa cells

Zahn, C., Hommel, A., Lu, L., Hong, W., Walther, D. J., Florian, S., et al. (2006). Knockout of Arfrp1 leads to disruption of ARF-like1 (ARL1) targeting to the trans-Golgi in mouse embryos and HeLa cells. Molecular Membrane Biology, 23, 475-485. doi:10.1080/09687860600840100.

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Genre: Journal Article
Alternative Title : Mol. Membr. Biol.

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 Creators:
Zahn, Claudia, Author
Hommel, Angela, Author
Lu,, Lei, Author
Hong, Wanjin, Author
Walther, Diego J.1, Author           
Florian, Simone, Author
Joost, Hans-Georg, Author
Schürmann, Annette, Author
Affiliations:
1Dept. of Human Molecular Genetics (Head: Hans-Hilger Ropers), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433549              

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Free keywords: ARF-like GTPases, trans-Golgi, embryogenesis, RNA interference
 Abstract: 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.

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Language(s): eng - English
 Dates: 2006-12-01
 Publication Status: Issued
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 Identifiers: eDoc: 309224
DOI: 10.1080/09687860600840100
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Title: Molecular Membrane Biology
  Alternative Title : Mol. Membr. Biol.
Source Genre: Journal
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Pages: - Volume / Issue: 23 Sequence Number: - Start / End Page: 475 - 485 Identifier: ISSN: 1464-5203