Bo Segerman, Per Holmfeldt, Justin Morabito, Lynne Cassimeris, and Martin Gullberg
The N-terminus of Op18/stathmin functionally interacts with tubulin heterodimers and is sufficient for phosphorylation-responsive microtubule-regulation.
J. Cell Science 2003 116:197

Abstract:
Op18 is the prototypical member of a family of phosphorylation-responsive regulators of microtubule (MT) dynamics. Previous dissection of Op18 has suggested that it has a functional dichotomy in which an intact N-terminus is required for catastrophe promotion (i.e. transition from growing to shrinking MTs), whereas an intact C-terminus is required for efficient ternary Op18-tubulin complex formation and the resultant tubulin-sequestering activity. Here we have expressed and functionally analyzed the properties of the N-terminus of Op18. The data show that the N-terminal 57 residues are sufficient for low-affinity tubulin interactions, as shown by inhibition of basal GTP hydrolysis of soluble heterodimers. In addition, high concentrations of the Op18 N-terminal portion increased the catastrophe rate during MT assembly in vitro. Overexpression of the N-terminus in a human cell line results in MT destabilization in interphase and phosphorylation-modulated accumulation of metaphase-arrested cells with dense short MTs. These results demonstrate that the N-terminus of Op18 has autonomous activity. Evidently, this activity is enhanced by the increase in tubulin affinity that is provided by the extended alpha-helical portion of native Op18.
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