| 1996 |
Rat Arl1 (rArl1) is a 22 kDa Ras-like small GTPase that localizes to the Golgi complex, co-localizing with mannosidase II and p28. Its Golgi association requires N-terminal myristoylation (inferred from BFA redistribution kinetics distinct from ARF/beta-COP). Recombinant GST-rArl1 binds GTP-γ-S in a dose-dependent manner, confirming GTP-binding activity. |
Immunofluorescence co-localization, GST-pulldown GTP-binding assay, BFA treatment, subcellular fractionation |
Journal of cell science |
Medium |
8834805
|
| 2001 |
ARL1 enriches at the trans-Golgi (AP-1-marked side). Golgi association requires N-terminal myristoylation. Dominant-negative ARL1(T31N) (GDP-restricted) causes disappearance of Golgi structure, while constitutively active ARL1(Q71L) (GTP-restricted) expands the Golgi into a vesicle-tubule network, stably recruits COPI and AP-1 coats, and arrests VSV-G transport. GTP-bound Arl1 interacts with arfaptin-2/POR1 but not GGA1. |
Dominant-negative/constitutively active mutant overexpression, immunofluorescence, subcellular fractionation, co-immunoprecipitation |
Journal of cell science |
High |
11792819
|
| 2001 |
ARL1 shares effectors with ARFs: MKLP1 and arfaptin2/POR1 bind ARL1 but not ARL2 or ARL3. Two-hybrid screens identified specific ARL1-binding proteins SCOCO and Golgin-245. SCOCO Golgi membrane binding is reversed by brefeldin A, suggesting a BFA-sensitive ARL1 exchange factor exists. Expression of [Q71L]ARL1 alters Golgi structure similarly to [Q71L]ARF1. |
Yeast two-hybrid, co-immunoprecipitation, brefeldin A treatment, overexpression in mammalian cells |
The Journal of biological chemistry |
High |
11303027
|
| 2002 |
In S. cerevisiae, loss of ARL1 causes defects in membrane traffic: reduced protein secretion, missorting of carboxypeptidase Y (CPY) to the vacuole, and reduced fluid-phase endocytosis (lucifer yellow uptake). Temperature-sensitive growth of arl1Δ ssd1 is suppressed by YPT1 (yeast Rab1a homolog), indicating partially overlapping functions. |
Gene deletion, radiolabeled secretion assay, vacuolar protein sorting assay, lucifer yellow uptake, genetic epistasis/suppression |
Yeast |
High |
12210899
|
| 2002 |
A point mutation in ARL1 (dlp2 allele) in S. cerevisiae causes defects in central vacuole formation due to aberrant membrane trafficking (many small vesicles instead of large central vacuoles), without affecting protein sorting to vacuoles. This ARL1 mutation also inhibits progression of autophagic cell death and Bax-induced apoptotic cell death. |
Genetic mapping, morphological analysis (electron microscopy), biochemical assays of vacuole function, Bax overexpression |
Cell death and differentiation |
Medium |
11840166
|
| 2004 |
Yeast ARL1 controls K+ influx: arl1 mutants show reduced 86Rb+ uptake (~30-40% less) and increased 14C-methylammonium internalization (consistent with plasma membrane hyperpolarization), while K+ and H+ efflux are normal. Overexpression suppressors include HAL4 and HAL5 (Ser/Thr kinases regulating K+-influx mediators Trk1p/Trk2p), placing ARL1 upstream of HAL4/HAL5 in K+ homeostasis. |
Radiolabeled ion uptake assays (86Rb+, 14C-methylammonium), high-copy suppressor screen, genetic analysis |
Journal of cell science |
Medium |
15126631
|
| 2005 |
T. brucei ARL1 is expressed only in the mammalian bloodstream form, localizes to the Golgi apparatus, and is essential for viability. RNAi depletion of TbARL1 causes Golgi disintegration and delay in exocytosis of GPI-anchored VSG to the parasite surface. |
RNAi knockdown, immunofluorescence localization, VSG exocytosis assay |
Biochemical Society transactions |
Medium |
16042563
|
| 2006 |
ARFRP1 (GTP-bound form) controls Golgi targeting of ARL1 and its effector Golgin-245. ARFRP1-T31N (dominant-negative) or RNAi depletion of ARFRP1 displaces ARL1 and Golgin-245 from the Golgi and alters syntaxin 6 distribution, while GM130 and giantin targeting are unaffected. In Arfrp1-/- embryos, ARL1 dislocates from Golgi membranes. |
Dominant-negative/constitutively active mutant overexpression, RNAi, immunofluorescence, mouse knockout embryo analysis |
Molecular membrane biology |
High |
17127620
|
| 2006 |
In plant (Arabidopsis/tobacco) cells, ARL1 GTP-bound form is required for recruitment of a GRIP-domain golgin to the Golgi. Site-directed mutagenesis of conserved residues in the GRIP domain of golgin and in ARL1 abolishes ARL1-GRIP interaction and redistributes GRIP to the cytosol, confirming direct ARL1–GRIP interaction is required for Golgi localization of the golgin. |
Live cell imaging, site-directed mutagenesis, GFP localization in plant cells |
Plant molecular biology |
Medium |
16830178
|
| 2008 |
Leishmania ARL-1 localizes to the TGN via N-terminal myristoylation (essential for localization). The dominant-negative empty-form mutant LdARL-1/T34N inhibits endocytosis and intracellular trafficking from TGN to the lysosome/multivesicular tubule and to acidocalcisomes, likely through mislocalisation of GRIP-domain vesicle tethering factors. |
Expression of GTP/GDP-locked and nucleotide-free mutants, fluorescence localization, endocytosis assays |
PloS one |
Medium |
18286177
|
| 2009 |
ARL1 and ARFRP1 have differential roles in TGN trafficking in mammalian cells: ARL1 knockdown specifically impairs retrograde transport of Shiga toxin to the TGN (via a SNARE complex containing Vti1a, syntaxin 6, and syntaxin 16), while ARFRP1 knockdown impairs anterograde transport of VSVG from the TGN. |
siRNA knockdown, Shiga toxin retrograde transport assay, VSVG anterograde transport assay, SNARE complex analysis |
The Journal of biological chemistry |
High |
19224922
|
| 2009 |
Endogenous GCC185 Golgi recruitment does not require Rab6A/A' or Arl1 in mammalian cells. Depletion of both Rab6A/A' and Arl1 had no effect on localization of endogenous GCC185 or its isolated GRIP domain. |
Knockdown by siRNA, immunofluorescence of endogenous proteins, yeast two-hybrid |
Cell |
Medium |
19703403
|
| 2011 |
Arfaptins (arfaptin-1 and arfaptin-2) associate with trans-Golgi membranes through interaction with Arl1 (not Arfs) via their BAR domain-containing region. Arfaptins compete with golgin-97 and golgin-245 for Arl1 binding. Time-lapse imaging shows arfaptins, but not golgin-97, are incorporated into vesicular/tubular structures emanating from the Golgi, suggesting Arl1 recruits arfaptins to the trans-Golgi for membrane deformation. |
Co-immunoprecipitation, siRNA knockdown, live cell time-lapse imaging, domain mapping |
The Journal of biological chemistry |
High |
21239483
|
| 2011 |
In yeast, the GAP Gcs1 acts on Arl1; loss of Gcs1 causes cold-sensitive growth and impaired endosomal transport through dysregulated (hyperactive) Arl1. Deletions in the Arl1 or Ypt6 vesicle-tethering pathways restore growth and trafficking in gcs1Δ by preventing Arl1 activation. Increased abundance of the Arl1 effector Imh1 also restores growth through Arl1 binding, suggesting excess active Arl1 sequesters proteins at the trans-Golgi membrane. |
Genetic epistasis, gene deletion, in vitro GAP assay, overexpression studies |
Molecular biology of the cell |
Medium |
21562219
|
| 2012 |
The small G protein Arl1 directs trans-Golgi-specific targeting of Arf1 exchange factors BIG1 and BIG2 (but not GBF1) in mammalian cells. Using Drosophila, Arl1 was found to bind directly to Sec71 (BIG1/2 ortholog) via an N-terminal region of Sec71. This establishes a pathway in which Arl1 recruits BIG1/BIG2 specifically to the trans-Golgi, thereby activating Arf1 at the trans-side. |
Liposome-based affinity purification, direct binding assay, siRNA knockdown in mammalian cells, immunofluorescence |
The Journal of cell biology |
High |
22291037
|
| 2012 |
In yeast, Arl1 has at least three functional conformations in vivo. The GTP-restricted allele ARL1[Q72L] complements membrane traffic (CPY secretion) but not K+ homeostasis, while the XTP-restricted allele ARL1[D130N] complements ion phenotypes but not membrane traffic. ARL1[F52G] and ARL1[Y82G] mutations (predicted to disrupt Imh1 GRIP domain binding) fail to complement both phenotypes. MON2 functions as a negative regulator of the GTP-restricted form of Arl1. |
Site-directed mutagenesis, allele-specific complementation, CPY secretion assay, ion sensitivity assays, genetic interaction analysis |
FEMS yeast research |
Medium |
22594927
|
| 2014 |
In Drosophila, Arl1 is essential for recruitment of three of four GRIP-domain golgins to the Golgi. Loss of Arl1 causes dispersal of AP-1 (a clathrin adaptor requiring Arf1 for membrane recruitment) at the trans-Golgi and complete failure of secretory granule biogenesis in larval salivary glands, establishing Arl1 as required to enhance Arf1 activation at the trans-Golgi in specific tissues. |
Loss-of-function clonal analysis, immunofluorescence, salivary gland morphology/secretion assay |
Journal of cell science |
High |
24610947
|
| 2015 |
Arfaptin-1 acts as a negative regulator of Arl1-mediated retrograde transport. Knockdown of arfaptin-1 accelerates retrograde transport of Shiga toxin B from endosomes to the Golgi, while overexpression inhibits it; an Arl1-binding-defective mutant (arfaptin-1b-F317A) fails to inhibit transport. Arfaptin-1 and golgin-97/golgin-245 do not interfere with each other's TGN localization, suggesting distinct Arl1-containing complexes in separate microdomains. |
siRNA knockdown, Shiga toxin transport assay, overexpression of wild-type and binding-defective mutants, immunofluorescence |
PloS one |
Medium |
25789876
|
| 2015 |
In Drosophila, Arl1 and its guanine nucleotide exchange factor Gartenzwerg (Garz) function in the same pathway as Arfaptin to control synapse growth. Genetic epistasis and biochemical data demonstrate that Arl1 and Garz are required for Arfaptin function at the Golgi during presynaptic nerve terminal growth. |
Genetic epistasis, biochemical interaction assays, overexpression in Drosophila motor neurons |
Biology open |
Medium |
26116655
|
| 2016 |
In S. cerevisiae, Arl1 (along with Ypt6) is required for starvation-induced autophagy specifically under high-temperature stress. Both proteins are required for proper trafficking of Atg9 to the phagophore assembly site (PAS); their absence prevents autophagosome construction at restrictive temperature. Arl1 and Ypt6 participate in autophagy by targeting the GARP complex to the PAS to regulate anterograde trafficking of Atg9. |
Deletion mutants, autophagy-specific assays (GFP-Atg8, Pho8Δ60), Atg9 localization, degron-inducible double mutant construction |
Autophagy |
Medium |
27462928
|
| 2017 |
In yeast, the Arl3-Arl1 GTPase cascade cooperates with the COG complex subunit Cog8 to regulate selective autophagy (Cvt pathway) via Atg9 trafficking. arl3Δcog8Δ and arl1Δcog8Δ double mutants show profound defects in aminopeptidase I maturation. Atg9 accumulates at the late Golgi in these double mutants under normal (but not starvation) conditions, placing Arl1 upstream of Atg9 trafficking at the Golgi. |
Double-deletion genetics, aminopeptidase I maturation assay, Atg9 localization by fluorescence microscopy |
Traffic |
Medium |
28627726
|
| 2019 |
ARFRP1 functions as a master regulator upstream of both ARL1 and ARL5 to coordinate tethering factor recruitment to the TGN: ARFRP1 activates ARL1 (which recruits golgins) and ARL5 (which recruits GARP), and this bifurcated GTPase cascade is essential for delivery of retrograde cargos to the TGN. |
siRNA knockdown, epistasis analysis, retrograde cargo transport assays, immunofluorescence |
The Journal of cell biology |
High |
31575603
|
| 2019 |
In yeast, Arl1 and its effector golgin Imh1 can suppress Ypt6 dysfunction in retrograde endosome-to-TGN transport. Overexpression of Arl1 or Imh1 restores GARP complex localization to the TGN in ypt6Δ cells. The N-terminal domain of Imh1 is critical for restoring GARP localization and endosome-to-TGN transport in the absence of Ypt6. |
Overexpression rescue genetics, GARP localization assay, retrograde transport assay, domain deletion analysis |
Molecular biology of the cell |
Medium |
30726160
|
| 2020 |
H2O2-induced oxidative stress causes protease-dependent degradation of Arl1 in HeLa cells, leading to dissociation of GRIP-domain proteins Golgin-97 and Golgin-245 from the trans-Golgi, loss of trans-Golgi cisternae, and inhibition of both anterograde and retrograde protein transport. ROS scavenger N-acetyl cysteine or protease inhibitors rescue Arl1 levels and Golgi function. |
H2O2 treatment, immunofluorescence, protease inhibitor rescue, ROS scavenger rescue, electron microscopy |
Molecular biology of the cell |
Medium |
32583744
|
| 2021 |
ARG2 interacts with ARL1 (identified by yeast two-hybrid assay). ARL1 knockdown inhibits autophagy while ARL1 overexpression promotes it in dermal fibroblasts, placing ARL1 downstream of ARG2 in autophagy regulation. |
Yeast two-hybrid, siRNA knockdown, overexpression, autophagy assays in fibroblasts |
Antioxidants |
Low |
34943028
|
| 2024 |
Cryo-EM structures of full-length Gea2 and the Arl1-Gea2 complex reveal that: (1) Gea2 forms a stable dimer via DCB and HUS domain interfaces; (2) Arl1 binds to the outer surface of the Gea2 DCB domain (not the dimerization surface), leaving the Gea2 dimer intact; (3) the interaction involves the classic FWY aromatic residue triad and two Arl1-specific residues; (4) mutations disrupting the Arl1-Gea2 interface abolish Imh1 Golgi association. |
Cryo-EM structure determination, mutagenesis, Imh1 Golgi localization assay |
Nature communications |
High |
38431634
|