Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 11 May 2004
Vol. 2004, Issue 232, p. tw166
[DOI: 10.1126/stke.2322004TW166]


TRAFFICKING Arls Well That Ends with Acetylation

ARF (adenosine diphosphate-ribosylation factor)-family small guanosine triphosphatases (GTPases) bind to the membranes of organelles and recruit effector proteins, thereby playing a key role in membrane trafficking. Membrane recruitment of ARFs depends on myristoylation of a glycine near the N terminus, which mediates a weak interaction with membrane lipids that enables the GDP-bound protein to associate with guanine nucleotide exchange factors and undergo conversion into the GTP-bound form that is tightly associated with the membrane (see Jackson). However, one member of this family, Arl3p, which is associated with the Golgi in yeast, lacks this glycine, and the mechanism whereby it is recruited has been unclear. Two groups, Behnia et al. and Setty et al., used a combination of techniques including gene deletion, mutational analysis, mass spectrometry, chemical cross-linking, and expression of fluorescently tagged proteins to investigate Arl3p targeting. Both groups determined that Arl3p localization depended on acetylation of a hydrophobic residue near the N terminus by the NatC N-terminal acetyltransferase complex and required the Golgi-localized integral membrane protein Sys1p. Setty et al. showed that Arl3p association with Sys1p depended on acetylation but not on its ability to bind or hydrolyze GTP. Behnia et al. expressed a mutated variant of human Sys1p that was retained in the endoplasmic reticulum in COS cells and showed redistribution of ARFRP1 (the human homolog of Arl3) to the endoplasmic reticulum, again independent of its ability to bind GTP. Thus, unlike the ARF proteins, Arl3p recruitment and binding does not require myristoylation-dependent association with membrane lipids but acetylation-dependent association with a specific receptor and is, moreover, independent of GTP-binding.

C. L. Jackson, N-terminal acetylation targets GTPases to membranes. Nat. Cell Biol. 6, 379-380 (2004). [Online Journal]

R. Behnia, B. Panic, J. R. Whyte, S. Munro, Targeting of the Arf-like GTPase Arl3p to the Golgi requires N-terminal acetylation and the membrane protein Sys1p. Nat. Cell Biol. 6, 405-413 (2004). [Online Journal]

S. R. G. Setty, T. I. Strochlic, A. H. Y. Tong, C. Boone, C. G. Burd, Golgi targeting of ARF-like GTPase Arl3p requires its Nα-acetylation and the integral membrane protein Sys1p. Nat. Cell Biol. 6, 414-419 (2004). [Online Journal]

Citation: Arls Well That Ends with Acetylation. Sci. STKE 2004, tw166 (2004).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882