Quantitative image analysis identifies pVHL as a key regulator of microtubule dynamic instability

Claudio R. Thoma, Alexandre Matov, Katrin L. Gutbrodt, Christian R. Hoerner, Zlatko Smole, Wilhelm Krek, Gaudenz Danuser

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Von Hippel-Lindau (VHL) tumor suppressor gene mutations predispose carriers to kidney cancer. The protein pVHL has been shown to interact with microtubules (MTs), which is critical to cilia maintenance and mitotic spindle orientation. However, the function for pVHL in the regulation of MT dynamics is unknown. We tracked MT growth via the plus end marker EB3 (end-binding protein 3)-GFP and inferred additional parameters of MT dynamics indirectly by spatiotemporal grouping of growth tracks from live cell imaging. Our data establish pVHL as a near-optimal MT-stabilizing protein: it attenuates tubulin turnover, both during MT growth and shrinkage, inhibits catastrophe, and enhances rescue frequencies. These functions are mediated, in part, by inhibition of tubulin guanosine triphosphatase activity in vitro and at MT plus ends and along the MT lattice in vivo. Mutants connected to the VHL cancer syndrome are differentially compromised in these activities. Thus, single cell-level analysis of pVHL MT regulatory function allows new predictions for genotype to phenotype associations that deviate from the coarser clinically defined mutant classifications.

Original languageEnglish (US)
Pages (from-to)991-1003
Number of pages13
JournalJournal of Cell Biology
Volume190
Issue number6
DOIs
StatePublished - Sep 20 2010

ASJC Scopus subject areas

  • Cell Biology

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