Role of ADP‐ribosylation factor domain protein 1 (ARD1/TRIM23) on lysosome biogenesis and function

These studies examine the regulation of adenylate cyclase in renal cortical membranes from phosphate-deprived and phosphate-deprived acidotic dogs. Enzyme stimulation by parathyroid hormone (PTH) was decreased in phosphate deprivation [Vmax 1,578 +/- 169 vs. 2,581 +/- 219 pmol adenosine 3',5'-cyclic monophosphate (cAMP).mg protein-1 x 30 min-1 in controls, P less than 0.01]. Metabolic acidosis further decreased PTH-stimulated activity. Membranes from phosphate-deprived dogs showed a decrease in Gs alpha-content by cholera toxin-dependent ADP-ribosylation (174 +/- 18 arbitrary units vs. 266.4 +/- 13.6 in controls, P less than 0.01). Metabolic acidosis further decreased Gs alpha-content, P less than 0.01. Gi content by pertussis-dependent ADP-ribosylation was also lower in phosphate-deprived and phosphate-deprived acidotic animals. Gs function was examined by its property to protect the catalytic unit from inactivation by N-ethylmaleimide when preincubated with GTP gamma S. In controls, protection of inactivation was 80% of the maximal activity, whereas in phosphate deprivation protection was less than 50%. In conclusion, metabolic acidosis enhances adenylate cyclase resistance to PTH in phosphate deprivation. These alterations are associated with a decrease in the content and function of Gs alpha, suggesting a role of Gs in the renal adaptation to phosphate depletion and acidosis.

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ADP-Ribosylation Factor (ARF) Interaction Is Not Sufficient for Yeast GGA Protein Function or Localization

Molecular Biology of the Cell ◽

10.1091/mbc.e02-02-0078 ◽

2002 ◽

Vol 13 (9) ◽

pp. 3078-3095 ◽

Cited By ~ 30

Author(s):

Annette L. Boman ◽

Paul D. Salo ◽

Melissa J. Hauglund ◽

Nicole L. Strand ◽

Shelly J. Rensink ◽

...

Keyword(s):

Membrane Trafficking ◽

Mammalian Cells ◽

Fluorescent Protein ◽

Protein Localization ◽

Carboxypeptidase Y ◽

Minor Role ◽

Temperature Sensitive ◽

Adp Ribosylation ◽

And Function ◽

Adp Ribosylation Factor

Golgi-localized γ-ear homology domain, ADP-ribosylation factor (ARF)-binding proteins (GGAs) facilitate distinct steps of post-Golgi traffic. Human and yeast GGA proteins are only ∼25% identical, but all GGA proteins have four similar domains based on function and sequence homology. GGA proteins are most conserved in the region that interacts with ARF proteins. To analyze the role of ARF in GGA protein localization and function, we performed mutational analyses of both human and yeast GGAs. To our surprise, yeast and human GGAs differ in their requirement for ARF interaction. We describe a point mutation in both yeast and mammalian GGA proteins that eliminates binding to ARFs. In mammalian cells, this mutation disrupts the localization of human GGA proteins. Yeast Gga function was studied using an assay for carboxypeptidase Y missorting and synthetic temperature-sensitive lethality between GGAs andVPS27. Based on these assays, we conclude that non-Arf-binding yeast Gga mutants can function normally in membrane trafficking. Using green fluorescent protein-tagged Gga1p, we show that Arf interaction is not required for Gga localization to the Golgi. Truncation analysis of Gga1p and Gga2p suggests that the N-terminal VHS domain and C-terminal hinge and ear domains play significant roles in yeast Gga protein localization and function. Together, our data suggest that yeast Gga proteins function to assemble a protein complex at the late Golgi to initiate proper sorting and transport of specific cargo. Whereas mammalian GGAs must interact with ARF to localize to and function at the Golgi, interaction between yeast Ggas and Arf plays a minor role in Gga localization and function.

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Role of ADP-ribosylation Factor 6 (ARF6) in Gastric Acid Secretion

Journal of Biological Chemistry ◽

10.1074/jbc.m305444200 ◽

2003 ◽

Vol 278 (38) ◽

pp. 36470-36475 ◽

Cited By ~ 22

Author(s):

Jun Matsukawa ◽

Kazuhisa Nakayama ◽

Taku Nagao ◽

Hidenori Ichijo ◽

Tetsuro Urushidani

Keyword(s):

Acid Secretion ◽

Gastric Acid Secretion ◽

Gastric Acid ◽

Adp Ribosylation ◽

Adp Ribosylation Factor

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Characterization of a GDP Dissociation Inhibitory Region of ADP-ribosylation Factor Domain Protein ARD1

Journal of Biological Chemistry ◽

10.1074/jbc.272.40.25077 ◽

1997 ◽

Vol 272 (40) ◽

pp. 25077-25082 ◽

Cited By ~ 12

Author(s):

Nicolas Vitale ◽

Joel Moss ◽

Martha Vaughan

Keyword(s):

Adp Ribosylation ◽

Inhibitory Region ◽

Domain Protein ◽

Adp Ribosylation Factor

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Erratum to “The role of ADP-ribosylation factor and SAR1 in vesicular trafficking in plants”[Biochim. Biophys. Acta Biomembr. 1664 (2004) 9–30]

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/s0005-2736(04)00207-x ◽

2004 ◽

Vol 1665 (1-2) ◽

pp. 201-201

Author(s):

A MEMON

Keyword(s):

Vesicular Trafficking ◽

Adp Ribosylation ◽

Adp Ribosylation Factor

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ADP-Ribosylation Factor 6 and a Functional PIX/p95-APP1 Complex Are Required for Rac1B-mediated Neurite Outgrowth

Molecular Biology of the Cell ◽

10.1091/mbc.e02-07-0406 ◽

2003 ◽

Vol 14 (4) ◽

pp. 1295-1307 ◽

Cited By ~ 73

Author(s):

Chiara Albertinazzi ◽

Lorena Za ◽

Simona Paris ◽

Ivan de Curtis

Keyword(s):

Membrane Trafficking ◽

Functional Connection ◽

Actin Organization ◽

Neurite Extension ◽

Adp Ribosylation ◽

Carboxy Terminal ◽

Endocytic Vesicles ◽

Adp Ribosylation Factor ◽

Developing Nervous System

The mechanisms coordinating adhesion, actin organization, and membrane traffic during growth cone migration are poorly understood. Neuritogenesis and branching from retinal neurons are regulated by the Rac1B/Rac3 GTPase. We have identified a functional connection between ADP-ribosylation factor (Arf) 6 and p95-APP1 during the regulation of Rac1B-mediated neuritogenesis. P95-APP1 is an ADP-ribosylation factor GTPase-activating protein (ArfGAP) of the GIT family expressed in the developing nervous system. We show that Arf6 has a predominant role in neurite extension compared with Arf1 and Arf5. Cotransfection experiments indicate a specific and cooperative potentiation of neurite extension by Arf6 and the carboxy-terminal portion of p95-APP1. Localization studies in neurons expressing different p95-derived constructs show a codistribution of p95-APP1 with Arf6, but not Arf1. Moreover, p95-APP1–derived proteins with a mutated or deleted ArfGAP domain prevent Rac1B-induced neuritogenesis, leading to PIX-mediated accumulation at large Rab11-positive endocytic vesicles. Our data support a role of p95-APP1 as a specific regulator of Arf6 in the control of membrane trafficking during neuritogenesis.

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Role of ARF-GEP100, a guanine nucleotide-exchange protein for ADP-ribosylation factor in macrophage phagocytosis

Inflammation and Regeneration ◽

10.2492/inflammregen.30.48 ◽

2010 ◽

Vol 30 (1) ◽

pp. 48-54

Author(s):

Akimasa Someya ◽

Isao Nagaoka

Keyword(s):

Guanine Nucleotide ◽

Nucleotide Exchange ◽

Adp Ribosylation ◽

Guanine Nucleotide Exchange ◽

Macrophage Phagocytosis ◽

Adp Ribosylation Factor ◽

Exchange Protein

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Abstract 536: Lysosome Insufficiency in Atherosclerosis Prone DBA/2 Mouse Macrophages Associated With Impaired Autolysosome Formation and Lipid Drop Clearance

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.536 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Peggy Robinet ◽

Jonathan D Smith

Keyword(s):

Cathepsin L ◽

Foam Cells ◽

Lysosomal Degradation ◽

Over Expression ◽

Protein Levels ◽

Lysosome Biogenesis ◽

Mouse Macrophages ◽

Macrophage Foam Cells ◽

And Function

In a previous study, we identified autolysosome formation as the limiting step for turnover of cholesterol esters in lipid droplets of macrophage foam cells from the atherosclerosis sensitive DBA/2 strain compared to the atherosclerosis resistant AKR mouse strain. As autophagosome formation was similar in these two strains, we wanted to evaluate the role of lysosome biogenesis and function on autolysosome formation in AKR and DBA/2 cells. The transcription factor TFEB is a key regulator for lysosome biogenesis and function that positively regulates the expression of lysosomal enzymes and structural proteins, and controls lysosomes number. For all our studies, we cultured AKR and DBA/2 macrophages with or without acetylated LDL (AcLDL) for 24h. First, we analyzed TFEB protein expression by western blot. Upon loading, TFEB was increased in AKR (48%, p<0.01) but not DBA/2 cells leading to a 45% higher TFEB level in AKR vs. DBA/2 foam cells (p<0.05), suggesting that lysosome number and function may be impaired in DBA/2 foam cells. To assess lysosome function and number, cells were labeled with Lysotracker red DND-99 (LyT) and analyzed by flow cytometry. We found that AcLDL loading did not affect LyT intensity. However, in both unloaded and loaded conditions, DBA/2 cells exhibited a 30 to 50% lower LyT intensity suggesting that they have intrinsically decreased lysosome number/function. Lysosomal degradation capacity was assayed by incubation with DQ-ovalbumin and we observed a 27% decrease in lysosome function in DBA/2 vs. AKR foam cells (p<0.01). In addition, upon loading, the mature form of cathepsin L was increased in AKR (43%, p<0.05) but not DBA/2 cells. Together these data suggest an impairment of lysosomal degradation capacity in DBA/2 foam cells. Finally, we investigated the role of TPC2, a lysosomal membrane protein which over expression has been previously linked to a defect in autolysosome formation. We found that upon AcLDL loading TPC2 protein levels were increased by 35% in DBA/2 cells, which are defective in autolysosome formation, while they were unchanged in AKR cells. In conclusion, we found that DBA/2 vs. AKR foam cells express more TPC2 and have fewer and/or dysfunctional lysosomes that may explain the autolysosome formation defect in these cells.

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