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© The Rockefeller University Press, 0021-9525/1999//1289 $5.00
The Journal of Cell Biology, Volume 146, Number 6, , 1999 1289-1302

Original Article

Op18/Stathmin Mediates Multiple Region-Specific Tubulin and Microtubule-Regulating Activities



Niklas Larssona, Bo Segermana, Bonnie Howellb, Kajsa Fridella, Lynne Cassimerisb, and Martin Gullberga

a Department of Cell and Molecular Biology, University of Umeå, Sweden
b Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania
Department of Cell and Molecular Biology, University of Umeå, S-901 87 Umeå, Sweden.46-90-77142046-90-7852532

martin.gullberg{at}cmb.umu.se

Oncoprotein18/stathmin (Op18) is a regulator of microtubule (MT) dynamics that binds tubulin heterodimers and destabilizes MTs by promoting catastrophes (i.e., transitions from growing to shrinking MTs). Here, we have performed a deletion analysis to mechanistically dissect Op18 with respect to (a) modulation of tubulin GTP hydrolysis and exchange, (b) tubulin binding in vitro, and (c) tubulin association and MT-regulating activities in intact cells. The data reveal distinct types of region-specific Op18 modulation of tubulin GTP metabolism, namely inhibition of nucleotide exchange and stimulation or inhibition of GTP hydrolysis. These regulatory activities are mediated via two-site cooperative binding to tubulin by multiple nonessential physically separated regions of Op18. In vitro analysis revealed that NH2- and COOH-terminal truncations of Op18 have opposite effects on the rates of tubulin GTP hydrolysis. Transfection of human leukemia cells with these two types of mutants result in similar decrease of MT content, which in both cases appeared independent of a simple tubulin sequestering mechanism. However, the NH2- and COOH-terminal–truncated Op18 mutants regulate MTs by distinct mechanisms as evidenced by morphological analysis of microinjected newt lung cells. Hence, mutant analysis shows that Op18 has the potential to regulate tubulin/MTs by more than one specific mechanism.

Key Words: microtubules • phosphoproteins • phenotype • signal transduction • GTP phosphohydrolase

© 1999 The Rockefeller University Press

1.used in this paper: AMP-PNP, adenyl-5'-yl imidodiphosphate; GST, glutathione-S-transferase; MT, microtubule; Op18, oncoprotein 18/stathmin

The present address for Bonnie Howell is Department of Biology, University of North Carolina, Chapel Hill, NC 27599.


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