Psychiatry related information on ARFGAP1

• Two clinically distinct phenotypes may be drawn, a mild mental retardation or a more complex and severe phenotype, according to the presence or absence of the CHRNA4 and ARFGAP1 genes respectively.European Journal of Human Genetics (2007) 15, 446-452. doi:10.1038/sj.ejhg.5201784; published online 7 February 2007 [1].

High impact information on ARFGAP1

• The paxillin LD4 domain mediates this reduction in Rac activity by recruiting an ADP-ribosylation factor GTPase-activating protein (Arf-GAP) that decreases Arf activity, thereby inhibiting Rac [2].
• In the context of biological Golgi membrane, both palmitoyl-coenzyme A (p-coA) and ARFGAP1, a GTPase-activating protein (GAP) for ADP-Ribosylation Factor 1, also participate in vesicle formation, but how their roles may be linked remains unknown [3].
• This role of BARS requires its interaction with ARFGAP1, which is in turn regulated oppositely by p-coA and nicotinamide adenine dinucleotide, which act as cofactors of BARS [3].
• Both PIKE-L and -A isoforms contain GTPase, pleckstrin homology (PH), ADP ribosylation factor-GTPase-activating protein, and two ankyrin repeats domains, and C-terminal ADP ribosylation factor-GTPase-activating protein activates its internal GTPase activity [4].
• 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 [5].

Biological context of ARFGAP1

• The addition of aluminium fluoride locks coatomer onto Golgi membranes and also decreases the binding kinetics of both ARF1 and ARFGAP1, suggesting that these proteins function in concert to mediate sorting and vesicle formation [6].
• The ARFGAP1 gene, which contained 16 exons ranging from 0.5 to 9.3 kb, was mapped to human chromosome 22q13.2-q13.3 using radiation hybridization and in silico analyses [7].
• The full-length cDNA for human ARFGAP1 was cloned following the identification of an EST obtained by large-scale cDNA library sequencing through a Blast search of public databases [7].
• Haploinsufficiency for CHRNA4 and ARFGAP1 may have contributed towards a severe phenotype [1].
• Phosphoinositide-dependent activation of the ADP-ribosylation factor GTPase-activating protein ASAP1. Evidence for the pleckstrin homology domain functioning as an allosteric site [8].

Anatomical context of ARFGAP1

• Using fluorescence-correlation spectroscopy, we found that most ARF1 and ARFGAP1 molecules are highly mobile in the cytosol (diffusion constant D approximately equal to 15 microm(2) s(-1)), whereas coatomer diffuses 5-10 times more slowly than expected (D approximately equal to 1 microm(2) s(-1)) [6].
• Interestingly, the expression of ARFGAP1 in testis is about sixfold higher than that in ovary, indicating a possible role of ARFGAP1 in the physiological function of sperm [7].
• Expression of ARFGAP1 in four human fetal tissues and seven cancer cell lines was also detected [7].
• ARFGAP1 is strongly expressed in endocrine glands and testis [7].
• AGAP1, an endosome-associated, phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton [9].

Physical interactions of ARFGAP1

• We concluded from these results that the Gap protein is not involved in S. aureus binding to human transferrin [10].

Other interactions of ARFGAP1

• The sorting scheme predicts a dependency on the amount of ARFGAP1 and explains the recent experimental findings that ARF-1 and COPI detach with different time constants from the Golgi membrane in vivo [11].
• Assay and properties of the GIT1/p95-APP1 ARFGAP [12].
• GIT1/p95-APP1 is an adaptor protein with an aminoterminal ARFGAP domain involved in the regulation of ARF6 function [12].
• Involvement of a novel ADP-ribosylation factor GTPase-activating protein, SMAP, in membrane trafficking: implications in cancer cell biology [13].
• An alpha4 integrin-paxillin-Arf-GAP complex restricts Rac activation to the leading edge of migrating cells [2].

Analytical, diagnostic and therapeutic context of ARFGAP1

• In order to initiate studies on the LHRH prohormone, three antisera (MC-1, MC-2 and MC-3) were generated using the human GAP (hGAP) 25-53 fragment as immunogen and a corresponding radioimmunoassay procedure was developed [14].

References