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.

Serine protease Htra1 associates with microtubules and inhibits cell migration / J. Chien, T. Ota, G. Aletti, R. Shridhar, M. Boccellino, L. Quagliuolo, A. Baldi, V. Shridhar. - In: MOLECULAR AND CELLULAR BIOLOGY. - ISSN 0270-7306. - 29:15(2009), pp. 4177-4187. [10.1128/MCB.00035-09]

Serine protease Htra1 associates with microtubules and inhibits cell migration

G. Aletti;
2009

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.
English
Molecular Biology; Cell Biology
Settore BIO/11 - Biologia Molecolare
Articolo
Esperti anonimi
Pubblicazione scientifica
2009
American Society for Microbiology
29
15
4177
4187
11
Pubblicato
Periodico con rilevanza internazionale
Aderisco
info:eu-repo/semantics/article
Serine protease Htra1 associates with microtubules and inhibits cell migration / J. Chien, T. Ota, G. Aletti, R. Shridhar, M. Boccellino, L. Quagliuolo, A. Baldi, V. Shridhar. - In: MOLECULAR AND CELLULAR BIOLOGY. - ISSN 0270-7306. - 29:15(2009), pp. 4177-4187. [10.1128/MCB.00035-09]
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262
Article (author)
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J. Chien, T. Ota, G. Aletti, R. Shridhar, M. Boccellino, L. Quagliuolo, A. Baldi, V. Shridhar
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/574492
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