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Nature Cell Biology 6, 414–419 (1 May 2004) | doi:10.1038/ncb1121

Golgi targeting of ARF-like GTPase Arl3p requires its N|[alpha]|-acetylation and the integral membrane protein Sys1p

Subba Rao Gangi Setty , Todd I. Strochlic , Amy Hin Yan Tong , Charles Boone & Christopher G. Burd

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.