Cathepsin X binds to cell surface heparan sulfate proteoglycans

Cathepsin X binds to cell surface heparan sulfate proteoglycans

Autor Nascimento, F. D. Google Scholar
Rizzi, CCA Google Scholar
Nantes, I. L. Google Scholar
Stefe, L. Google Scholar
Turk, B. Google Scholar
Carmona, A. K. Google Scholar
Nader, H. B. Google Scholar
Juliano, L. Google Scholar
Tersariol, ILS Google Scholar
Instituição Univ Mogi Cruzes
Universidade Federal de São Paulo (UNIFESP)
Jozef Stefan Inst
Resumo Glycosaminoglycans have been shown to be important regulators of activity of several papain-like cathepsins. Binding of glycosaminoglycans to cathepsins thus directly affects catalytic activity, stability or the rate of autocatalytic activation of cathepsins. the interaction between cathepsin X and heparin has been revealed by affinity chromatography using heparin-Sepharose. Conformational changes were observed to accompany heparin-cathepsin X interaction by far UV-circular dichroism at both acidic (4.5) and neutral (7.4) pH. These conformational changes promoted a 4-fold increase in the dissociation constant of the enzyme-substrate interaction and increased 2.6-fold the k(cat) value also. the interaction between cathepsin X and heparin or heparan sulfate is specific since dermatan sulfate, chondroitin sulfate, and hyaluronic acid had no effect on the cathepsin X activity. Using flow cytometry cathepsin X was shown to bind cell surface heparan sulfate proteoglycans in wild-type CHO cells but not in CHO-745 cells, which are deficient in glycosaminoglycan synthesis. Moreover, fluorescently labeled cathepsin X was shown by confocal microscopy to be endocytosed by wild-type CHO cells, but not by CHO-745 cells. These results demonstrate the existence of an endocytosis mechanism of cathepsin X by the CHO cells dependent on heparan sulfate proteoglycans present at the cell surface, thus strongly suggesting that heparan sulfate proteoglycans can regulate the cellular trafficking and the enzymatic activity of cathepsin X. (c) 2005 Elsevier Inc. All rights reserved.
Palavra-chave heparin
heparin sulfate
cathepsin X
lysosomal enzyme
cysteine proteinase
Idioma Inglês
Data de publicação 2005-04-15
Publicado em Archives of Biochemistry and Biophysics. New York: Elsevier B.V., v. 436, n. 2, p. 323-332, 2005.
ISSN 0003-9861 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 323-332
Fonte http://dx.doi.org/10.1016/j.abb.2005.01.013
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000228225500012
Endereço permanente http://repositorio.unifesp.br/handle/11600/28250

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