The nanomechanics of polycystin-1 extracellular region

Feng Qian, Wen Wei, Gregory Germino, Andres Oberhauser

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Recent evidence suggests that polycystin-1 (PC1) acts as a mechanosensor, receiving signals from the primary cilia, neighboring cells, and extracellular matrix and transduces them into cellular responses that regulate proliferation, adhesion, and differentiation that are essential for the control of renal tubules and kidney morphogenesis. PC1 has an unusually long extracellular region (∼3000 amino acids) with a multimodular structure. Proteins with a similar architecture have structural and mechanical roles. Based on the structural similarities between PC1 and other modular proteins that have elastic properties we hypothesized that PC1 functions mechanically by providing a flexible and elastic linkage between cells. Here we directly tested this hypothesis by analyzing the mechanical properties of the entire PC1 extracellular region by using single molecule force spectroscopy. We show that the PC1 extracellular region is highly extensible and that this extensibility is mainly caused by the unfolding of its Ig-like domains. Stretching the native PC1 extracellular region results in a sawtooth pattern with equally spaced force peaks that have a wide range of unfolding forces (50-200 pN). By combining single-molecule force spectroscopy and protein engineering techniques, we demonstrate that the sawtooth pattern in native PC1 extracellular region corresponds to the sequential unfolding of individual Ig-like domains. We found that Ig-like domains refold after mechanical unfolding. Hence, the PC1 extracellular region displays a dynamic extensibility whereby the resting length might be regulated through unfolding/refolding of its Ig-like domains. These force-driven reactions may be important for cell elasticity and the regulation of cell signaling events mediated by PC1.

Original languageEnglish (US)
Pages (from-to)40723-40730
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number49
DOIs
StatePublished - Dec 9 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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