ADP-ribosylation of tubulin by chicken NAD-arginine ADP-ribosyltransferase suppresses microtubule formation.

We obtained evidence that tubulin and actin, two major cytoskeletal proteins, are preferentially ADP-ribosylated in the bovine brain cytosol by NAD-arginine ADP-ribosyltransferase purified from chicken polymorphonuclear leukocytes. ADP-ribosylation of tubulin almost completely blocked self-assembly of the protein. The stoichiometry of ADP-ribose incorporation into unassembled and assembled tubulin was 6 and 2 mol/mol of tubulin, respectively. These findings suggest that sites of ADP-ribosylation in the unassembled tubulin molecule are crucial for tubulin assembly, and that covalently attached ADP-ribose moieties interfere with tubulin interaction by steric hindrance or conformational change. Thus, ADP-ribosylation may be involved in cytoskeletal organization in the brain via the modification of tubulin.