High impact information on ARL1

• Golgi targeting of ARF-like GTPase Arl3p requires its Nalpha-acetylation and the integral membrane protein Sys1p [1].
• We find that Rud3p is localized to the Golgi via a COOH-terminal domain that is distantly related to the GRIP domain that recruits several coiled-coil proteins to the trans-Golgi by binding the small Arf-like GTPase Arl1p [2].
• Thus, Neo1p, Ysl2p, and Arl1p represent three proteins that collaborate in membrane trafficking within the endosomal/Golgi system [3].
• Yeast Ysl2p, homologous to Sec7 domain guanine nucleotide exchange factors, functions in endocytosis and maintenance of vacuole integrity and interacts with the Arf-Like small GTPase Arl1p [4].
• We provide multiple genetic and biochemical evidence for an interaction between Ysl12p and the Arf-like protein Arl1p, consistent with a potential function as an Arf guanine nucleotide exchange factor (GEF) [4].

Biological context of ARL1

• Although loss of ARL1 confers several phenotypes, including sensitivity to hygromycin B and Li(+), reduced influx of K(+), and increased secretion of carboxypeptidase Y (CPY), loss of ATC1 was without effect by these and other measures [5].
• The yeast genes, ARL1 and CCZ1, interact to control membrane traffic and ion homeostasis [6].
• The yeast ARL1 gene, encoding a guanine-nucleotide binding protein of the Arf-like family, exhibits a synthetic genetic interaction with CCZ1 [6].
• Consistent with the idea that Ysl2p and Arl1p have closely related functions, Delta arl1 cells are defective in endocytic transport and in vacuolar protein sorting [4].
• Our data are consistent with the conclusion that Arl1p moves in a dynamic equilibrium between trans-Golgi and cytosol, and the release of Arl1p from membranes in cells requires the hydrolysis of bound GTP, which is accelerated by Gcs1p [7].

Anatomical context of ARL1

• Arl1p was observed both on trans-Golgi and in cytosol and was recruited from cytosol to membranes in a GTP-dependent manner [7].
• The yeast and mammalian Arl1 proteins bind to the Golgi complex, where they recruit specific structural proteins such as Golgins [8].
• The arl1 mutant strain internalized approximately 25% more [(14)C]-methylammonium ion than did the wild type, consistent with hyperpolarization of the plasma membrane [9].
• We generated dominant negative mutant forms of Arf 1 and Arf3 and examined their effect on trafficking of reporter proteins in protoplasts [10].

Associations of ARL1 with chemical compounds

• The arl1 mutant was sensitive to toxic cations, including hygromycin B and other aminoglycoside antibiotics, tetramethylammonium ions, methylammonium ions and protons [9].
• An arl1 Delta ccz1 Delta double mutant was viable but grew slowly, was more sensitive to caffeine, Ca(2+), Zn(2+), and hygromycin B than either single mutant, and had a more severe vacuolar protein sorting phenotype [6].

Physical interactions of ARL1

• In vitro binding experiments demonstrated that activated Arl1p-GTP binds specifically and directly to the Imh1p GRIP domain [11].
• Arl1p is involved in transport of the GPI-anchored protein Gas1p from the late Golgi to the plasma membrane [12].

Regulatory relationships of ARL1

• Overexpression of ARL1 did not suppress ccz1 Delta mutant phenotypes, nor did overexpression of CCZ1 suppress arl1 Delta mutant phenotypes [6].
• Golgi recruitment of GRIP domain proteins by Arf-like GTPase 1 is regulated by Arf-like GTPase 3 [11].

Other interactions of ARL1

• The ts phenotype of the arl1deltassd1 strain was suppressed by YPT1, the yeast Rab1a homologue, suggesting that ARL1 and YPT1 have partially overlapping functions [13].
• Role for Gcs1p in regulation of Arl1p at trans-Golgi compartments [7].
• Additionally, expression of ENA1, the Na(+)/Li(+) efflux ATPase, and activated calcineurin, but not normal calcineurin, suppressed the Li(+)-sensitive phenotype of the arl1 atc1 double mutant [5].
• These results are consistent with a model in which ARL1, via regulation of HAL4/HAL5, governs K(+) homeostasis in cells [9].
• The similar requirements for localization of GRIP domains from yeast, mouse, and human when expressed in yeast, and the presence of Arl1p and Arl3p homologs in these species, suggest that this is an evolutionarily conserved mechanism [11].

Analytical, diagnostic and therapeutic context of ARL1

• A family of three structurally related proteins were cloned from human cDNA libraries by their ability to interact preferentially with the activated form of human ADP-ribosylation factor 3 (ARF3) in two-hybrid assays [14].

References