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The human protein, ARNO, includes Sec7 and carboxy-terminal pleckstrin-homology (PH) domains stimulating guanine-nucleotide exchange on ARF1. The PH domain uses the negatively charged phospholipid vesicles supplemented with phosphatidylinositol biphosphate to mediate an increase in the ARNO exchange activity. Brefeldin A fails to suppress the exchange activity of ARNO. This reveals the presence of a regulatory component, associating with ARNO, which is sensitive to brefeldin A.

Inhibition of protein transport out of the Golgi apparatus by Brefeldin A (BRA) leads to the disassembly of organelles in mammalian cells. BFA blocking results in the release of the non-clathrin coat from Golgi vesicles and membranes. The elucidation of BFA function in Saccharomyces cerevisiae using genetic methods reveals that cell growth is stopped when BFA is added to the Saccharomyces cerevisiae cell strains.

The authors discuss ADP-ribosylation factor proteins. The topics of interest include the involvement of mammalian ADP-ribosylation factor - guanine-nucleotide exchange factors in coat recruitment to endosomes and sorting in polarized cells.

The plant hormone auxin is transported in a polar manner along the shoot-root axis, which requires efflux carriers such as PIN1. Asymmetric localization of PIN1 develops from a random distribution in Arabidopsis early embryogenesis. Coordinated polar localization of PIN1 is defective in gnom embryos. GNON is a membrane-associated guanine-nucleotide exchange factor on ADP-ribosylation factor G protein (ARF GEF). Thus, GNOM-dependent vesicle trafficking may establish cell polarity, resulting in polar auxin transport., Polar auxin transport has been implicated in a variety of developmental processes, including phototropism, gravitropism, apical dominance, root formation, and vascular tissue patterning (1, 2). These vectorial processes require coordinated [...]

The hepatitis E virus (HEV) genome is a single-stranded, positive-sense RNA that encodes three proteins including the ORF1 replicase. Mechanisms of HEV replication in host cells are unclear, and only a few cellular factors involved in this step have been identified so far. Here, we used brefeldin A (BFA) that blocks the activity of the cellular Arf guanine nucleotide exchange factors GBF1, BIG1, and BIG2, which play a major role in reshuffling of cellular membranes. We showed that BFA inhibits HEV replication in a dose-dependent manner. The use of siRNA and Golgicide A identified GBF1 as a host factor critically involved in HEV replication. Experiments using cells expressing a mutation in the catalytic domain of GBF1 and overexpression of wild type GBF1 or a BFA-resistant GBF1 mutant rescuing HEV replication in BFA-treated cells, confirmed that GBF1 is the only BFA-sensitive factor required for HEV replication. We demonstrated that GBF1 is likely required for the activity of HEV replication complexes. However, GBF1 does not colocalise with the ORF1 protein, and its subcellular distribution is unmodified upon infection or overexpression of viral proteins, indicating that GBF1 is likely not recruited to replication sites. Together, our results suggest that HEV replication involves GBF1-regulated mechanisms. [ABSTRACT FROM AUTHOR]