ADP‐ribosylation factor (ARF)‐like 4, 6, and 7 represent a subgroup of the ARF family characterized by rapid nucleotide exchange and a nuclear localization signal

Abstract

The novel ARF-like GTPase ARL7 is a close relative of ARL4 and ARL6 (71% and 59% identical amino acids). A striking characteristic of these GTPases is their basic C-terminus which, when fused to the C-terminus of green fluorescent protein (GFP), targets the constructs to the nucleus of transfected COS-7 cells. Full length ARL4 was detected in both nuclear and extranuclear compartments, whereas a construct of ARL4 lacking its C-terminus was excluded from the nucleus. Nucleotide exchange rates of recombinant ARL4, ARL6 and ARL7 were similar and appeared considerably higher than those of other members of the ARF family (ARF1, ARP). It is concluded that ARL4, ARL6 and ARL7 form a subgroup within the ARF family with similar, possibly nuclear, function.z 1999 Federation of European Biochemical Societies.

ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol loading and participates in apolipoprotein AI-dependent cholesterol export

“…The present results on intracellular localization and trafficking of ARL7 differ from a previous study which led to the assumption that ARL7 may be located in the nucleus [14]. This assumption based on the use of a synthetic construct consisting of GFP fused to the last 20 amino acids of the ARL7 carboxyterminus.…”

“…None of the various ARL7-EGFP fusion constructs that were used in our study were able to direct a significant fraction of the fusion proteins into the nucleus. Conversely, it could be demonstrated by immunocytochemistry that a fraction of ARL4, which is a close relative of ARL7, is in fact located in the nucleus of cultured Sertoli and neuroblastoma cells [14,30]. Thus, it cannot be excluded at present that the EGFP fusion at the carboxy-terminus of ARL7 that was used in our study inhibited its import into the nucleus.…”

“…The aim of the present study was to identify ARLs or ARFs which may be involved in cholesterol transport upon ABCA1-meditated cholesterol secretion. Our results indicate that, among a great variety of ARFs and ARLs, ARL7, which was cloned initially as a GTPase with rapid nucleotide exchange and a putative nuclear function [14], is the only family member whose expression is induced significantly by liver X-receptor (LXR) and retinoid X-receptor (RXR) agonists (T0901317 and RO-26-4456) or cholesterol-loading. Since this regulation implied that ARL7 may be involved in RCT, we studied its intracellular trafficking and the effect of several ARL7 mutants on apoAI-dependent cholesterol efflux.…”

The Arf Family GTPase Arl4A Complexes with ELMO Proteins to Promote Actin Cytoskeleton Remodeling and Reveals a Versatile Ras-binding Domain in the ELMO Proteins Family

“…The Arl4 family consists of three closely related members: A, C, and D (32). Unlike the other members of this family, Arl4s are preferentially GTPloaded because of their weak affinity for nucleotides and therefore exhibit high spontaneous nucleotide exchange rates (33). Recent reports suggest that Arl4s are involved in cytoskeletal rearrangement through their ability to bind the Arf6 guanine exchange factor, ARNO, and localize it to the cell periphery for Arf6 activation (24,30).…”

ARL4, an ARF-like Protein That Is Developmentally Regulated and Localized to Nuclei and Nucleoli

“…Expression of rat ARL4 was reported to be cell differentiation-dependent (4). Its role in adipocyte metabolism and sperm production was suggested (10) and nuclear localization of transiently expressed protein was demonstrated (11).…”