Different regions of mammalian adp-ribosylation factor 1 are required for activation by the goioi guanine nucleotide exchange factor and for promoting efficient AP-I recruitment

J. O. Lung, S. Kornfeld

Research output: Contribution to journalArticle

Abstract

ADP-nhosylation factor (ARF) is a small GTP binding protein th.it plays an essential role in clathrin-coated vesicle formation on Golgi membranes, a process which selectively diverts newly synthesized lysosomal en/ymes out of the secretory pathway and into a lysosomal targeting pathway. ÄRF is activated by a guanine nucleotide exchange factor (GEF) on the Golgi membrane, which catalyzes the exchange of GDP for GTP on ARF. Activated ARF binds to Golgi membranes and facilitates recruitment of AP-1 adaptors, components of the Golgi's clathrin coat. Although mammalian ARF1 imARFl ) and Sacchanimycei cerevisiae ARF2 lyARF2) are IT'-'i identical, only mARF! is activated by the rat liver Golgi GEF. Furthermore. mARF I promotes AP-I binding more efficiently than yARF2. even when coat protein recruitment is adjusted for the amount of ARF bound to the Golgi membranes Using chimeras generated between yARF2 and mARFl. we have mapped the niARFI domains important for activation by the rat liver Golgi GEF ami for efficient AP-1 recruitment. Although a peptide corresponding to amino acids (a.a. l 2-18 of mARFl inhibits activation of mARF 1 by Golsi membranes (Randazzo. P.A., Yang. Y.C.. Rulka. C. and R.A. Kahn (1993) J. Biol. Chemi. we found that the amino terminus (a.a. 2-34) of mARFl did not contain unique residues critical for activation by the Golgi GEF. Instead, a.a. 95-181 of mARFl contained the primary region required for activation by the GEF. A region delineated by a.a. 35-94 was required for efficient AP-1 recruitment As pan of this region of ARF corresponds to the ras effector domain, we hypothesize that it may contain an effector domain for ARF.

Original languageEnglish
Pages (from-to)A1235
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997
Externally publishedYes

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