Possible role of bars-50, a substrate of brefeldin A-dependent mono- ADP-ribosylation, in intracellular transport

Maria Giuseppina Silletta, Maria Di Girolamo, Giusy Fiucci, Roberto Weigert, Alexander Mironov, Maria Antonietta De Matteis, Alberto Luini, Daniela Corda

Research output: Contribution to journalArticlepeer-review

Abstract

Brefeldin A (BFA), a fungal metabolite that inhibits membrane transport, potently stimulates an endogenous ADP-ribosylation reaction that selectively modifies two cytosolic proteins of 38 and 50 kDa on an amino acid residue different from those used by all known mADPRTs. The 38-kDa substrate was identified as the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), whereas the 50-kDa substrate (BARS-50) was characterized as a novel guanine nucleotide binding protein. Thus, BARS-50 is able to bind GTP and its ADP-ribosylation is inhibited by the βγ subunit of GTP-binding (G) proteins. Moreover, BARS-50 was demonstrated to be a group of closely related proteins that appear to be different from all the known G proteins. A partially purified BARS-50 was obtained from rat brain cytosol, which was then used for microsequencing and in functional studies. A similar procedure led to the purification of native (non-ADP-ribosylated) BARS-50. The possible role of the BFA-dependent ADP-ribosylation and of BARS-50 in the maintenance of Golgi structure and function was addressed by examining which of the effects of BFA may be modified by inhibiting this reaction. We find that the BFA-dependent transformation of the Golgi stacks into a tubular reticular network is prevented when the BFA-dependent ADP-ribosylation activity was blocked by specific inhibitors thus indicating that BFA-dependent ADP- ribosylation of cytosolic proteins participate in the dynamic regulation of intracellular transport.

Original languageEnglish
Pages (from-to)321-330
Number of pages10
JournalAdvances in Experimental Medicine and Biology
Volume419
Publication statusPublished - 1997

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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