The parvulin-type peptidyl-prolyl
cis/trans isomerases (PPIases) have been shown to be involved in
tumor progression and the pathogenesis of
Alzheimer's disease and were therefore a subject of intense research. Here, we describe a role for
parvulin 17 in microtubule assembly. Co-precipitation experiments and sedimentation assays demonstrated that
parvulin 17 interacts with
tubulin in a
GTP-dependent manner and thereby promotes the formation of microtubules, as shown by transmission electron microscopy and a microtubule polymerization assay. The microtubule-assembly-promoting properties of
parvulin 17 seem to depend on its
PPIase activity. Thus, catalytic deficient variants of
parvulin 17 were not able to promote microtubule formation. Accordingly, inhibitors of
parvulin 17 activity also prevent parvulin-catalyzed
tubulin polymerization. The analysis of
tubulin interaction sites on parvulin using
peptide microarrays revealed that
tubulin interacts with the substrate binding pocket of parvulin. Additionally, β-
tubulin peptide scan on microarrays demonstrates interaction of
parvulin 17 with an
Arg-Pro-Asp motif corresponding to
proline residue 87 of β-
tubulin. Confocal
laser scanning microscopy points to a function of
parvulin 17 in microtubule dynamics as well.
Parvulin 17 is predominantly found in the cytosol and colocalizes with microtubules.