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Golgi targeting of ARF-like GTPase Arl3p requires its Nα-acetylation and the integral membrane protein Sys1p

Nature Cell Biology volume 6, pages 414–419 (2004)Cite this article

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Abstract

Myristoylation of ARF family GTPases is required for their association with Golgi and endosomal membranes, where they regulate protein sorting and the lipid composition of these organelles. The Golgi-localized ARF-like GTPase Arl3p/ARP lacks a myristoylation signal, indicating that its targeting mechanism is distinct from myristoylated ARFs. We demonstrate that acetylation of the N-terminal methionine of Arl3p requires the NatC Nα-acetyltransferase and that this modification is required for its Golgi localization. Chemical crosslinking and fluorescence microscopy experiments demonstrate that localization of Arl3p also requires Sys1p, a Golgi-localized integral membrane protein, which may serve as a receptor for acetylated Arl3p.

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Figure 1: Genes required for Golgi localization of GFP–GRIP and Arl1p–GFP identify candidate ARL pathway genes.
Figure 2: Arl3p(Q78L) rescues the growth defect of a ypt6Δ mutant and requires SYS1, MAK3 and MAK10 genes to be localized to the Golgi.
Figure 3: Acetylation of the amino-terminal methionine of Arl3p requires NatC Nα-acetyltransferase.
Figure 4: Chemical crosslinking identifies a complex containing Sys1p and Nα-acetylated Arl3p.

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  • 30 April 2004

    Amy Hin Yang to Amy Hin Yan

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Acknowledgements

We thank M. Marks, M. Chou, M. Lemmon, T. Graham, S. Emr and E. Bi for discussions, M. Chou for reading the manuscript, E. Bi and F. Luca for the use of their fluorescence microscopes, G. Van Duyne and J. Fields for the use of their cell lysis apparatus, and S. Munro for sharing unpublished information. We are indebted to C.-X. Yuan and the staff of the Proteomics Core Facility of the Genomics Institute and the Abramson Cancer Center, University of Pennsylvania, for assistance with the Arl3p mass spectrometry. This research was supported by a grant (GM61221) from the National Institutes of Health to C.G.B.

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Authors and Affiliations

  1. Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, 421 Curie Blvd. BRB 2/3 room 1010, Philadelphia, 19104-6058, PA, USA

    Subba Rao Gangi Setty, Todd I. Strochlic & Christopher G. Burd

  2. Banting and Best Department of Medical Research, University of Toronto, Toronto, M5G 1L6, ON, Canada

    Amy Hin Yan Tong & Charles Boone

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Correspondence to Christopher G. Burd.

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Setty, S., Strochlic, T., Tong, A. et al. Golgi targeting of ARF-like GTPase Arl3p requires its Nα-acetylation and the integral membrane protein Sys1p. Nat Cell Biol 6, 414–419 (2004). https://doi.org/10.1038/ncb1121

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