title: Parvulin 17 promotes microtubule assembly by its peptidyl-prolyl cis/trans isomerase activity.
abstract: 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.
authors.affiliation: Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, D-06120 Halle/Saale, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Thiele
authors.forename: Karolin
authors.initials: K
authors.lastname: Krentzlin
authors.forename: Frank
authors.initials: F
authors.lastname: Erdmann
authors.forename: David
authors.initials: D
authors.lastname: Rauh
authors.forename: Gerd
authors.initials: G
authors.lastname: Hause
authors.forename: Johannes
authors.initials: J
authors.lastname: Zerweck
authors.forename: Susann
authors.initials: S
authors.lastname: Kilka
authors.forename: Stephanie
authors.initials: S
authors.lastname: Pösel
authors.forename: Gunter
authors.initials: G
authors.lastname: Fischer
authors.forename: Mike
authors.initials: M
authors.lastname: Schutkowski
authors.forename: Matthias
authors.initials: M
authors.lastname: Weiwad
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D003078:Colchicine / Q000494:pharmacology; D006801:Humans; D008870:Microtubules / Q000378:metabolism*; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010446:Peptide Fragments / Q000378:metabolism*; D019696:Peptidylprolyl Isomerase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D058105:Polymerization; D011485:Protein Binding; D014404:Tubulin / Q000378:metabolism*; D050257:Tubulin Modulators / Q000494:pharmacology
chemical_list: D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D010446:Peptide Fragments; D014404:Tubulin; D050257:Tubulin Modulators; C000606846:PIN1 protein, human; C000606848:PIN4 protein, human; D019696:Peptidylprolyl Isomerase; D003078:Colchicine