RGD Reference Report - Arf-1 (ADP-ribosylation factor-1) is involved in the activation of a mammalian Na+-selective current. - Rat Genome Database

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Arf-1 (ADP-ribosylation factor-1) is involved in the activation of a mammalian Na+-selective current.

Authors: Straube, S  Parekh, AB 
Citation: Straube S and Parekh AB, Biochem J 2004 Jan 15;377(Pt 2):539-44.
RGD ID: 1302324
Pubmed: (View Article at PubMed) PMID:14563210
DOI: Full-text: DOI:10.1042/BJ20030824

Stimulation of mammalian cells often results in an increase in the intracellular Na(+) concentration, brought about by Na(+) influx into the cell via Na(+)-permeable ion channels. In some cell types, particularly renal epithelia and mast cells, non-hydrolysable analogues of GTP, such as GTP[S] (guanosine 5'-[gamma-thio]triphosphate), activate a non-voltage-activated Na(+)-selective current. We have carried out whole-cell patch-clamp experiments to examine how GTP[S] activates the Na(+) current in a rat mast cell line. The ability of GTP[S] to activate Na(+) influx was prevented by including GTP in the pipette solution, indicating the involvement of small G-proteins. Brefeldin A and Arf-1-(2-17), inhibitors of Arf-1 (ADP-ribosylation factor-1) proteins, suppressed the activation of Na(+) entry by GTP[S]. However, non-active succinylated Arf-1-(2-17) or an N-terminal myristoylated peptide directed towards Arf-5 were ineffective. Arf proteins modulate the cytoskeleton, and disruption of the cytoskeleton with cytochalasin D or its stabilization with phalloidin impaired the development of the Na(+) current. Disaggregation of microtubules was without effect. Dialysis with cAMP or inhibition of cAMP phosphodiesterase with caffeine both decreased the extent of Na(+) entry, and this was not prevented by pre-treatment with broad-spectrum protein kinase inhibitors. Collectively, our results suggest that the mechanism of activation of a mammalian non-voltage-activated Na(+)-selective current requires an Arf small G-protein, most probably Arf-1.

Annotation

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Arf1  (ADP-ribosylation factor 1)


Additional Information