Serine protease Htra1 associates with microtubules and inhibits cell migration

Jeremy Chien, Takayo Ota, Giovanni Aletti, Ravi Shridhar, Mariarosaria Boccellino, Lucio Quagliuolo, Alfonso Baldi, Viji Shridhar

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

HtrA1 belongs to a family of serine proteases found in organisms ranging from bacteria to humans. Bacterial HtrA1 (DegP) is a heat shock-induced protein that behaves as a chaperone at low temperature and as a protease at high temperature to help remove unfolded proteins during heat shock. In contrast to bacterial HtrA1, little is known about the function of human HtrA1. Here, we report the first evidence that human HtrA1 is a microtubule-associated protein and modulates microtubule stability and cell motility. Intracellular HtrA1 is localized to microtubules in a PDZ (PSD95, Dlg, ZO1) domain-dependent, nocodazole-sensitive manner. During microtubule assembly, intracellular HtrA associates with centrosomes and newly polymerized microtubules. In vitro, purified HtrA1 promotes microtubule assembly. Moreover, HtrA1 cosediments and copurifies with microtubules. Purified HtrA1 associates with purified α- and β-tubulins, and immunoprecipitation of endogenous HtrA1 results in coprecipitation of α-, β-, and γ-tubulins. Finally, downregulation of HtrA1 promotes cell motility, whereas enhanced expression of HtrA1 attenuates cell motility. These results offer an original identification of HtrA1 as a microtubule-associated protein and provide initial mechanistic insights into the role of HtrA1 in theregulation of cell motility by modulating microtubule stability.

Original languageEnglish (US)
Pages (from-to)4177-4187
Number of pages11
JournalMolecular and Cellular Biology
Volume29
Issue number15
DOIs
StatePublished - Aug 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Chien, J., Ota, T., Aletti, G., Shridhar, R., Boccellino, M., Quagliuolo, L., Baldi, A., & Shridhar, V. (2009). Serine protease Htra1 associates with microtubules and inhibits cell migration. Molecular and Cellular Biology, 29(15), 4177-4187. https://doi.org/10.1128/MCB.00035-09