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First published online 29 July 2008
doi: 10.1242/jcs.023721

Journal of Cell Science 121, 2652-2661 (2008)
Published by The Company of Biologists 2008
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Research Article

The role of cathepsin X in the migration and invasiveness of T lymphocytes

Zala Jevnikar1, Natasa Obermajer1, Matthew Bogyo2 and Janko Kos1,3,*

1 Faculty of Pharmacy, University of Ljubljana, Askerceva 7, 1000 Ljubljana, Slovenia
2 Department of Pathology, Stanford University, Stanford, CA 94305-5324, USA
3 Department of Biotechnology, Jozef Stefan Institute, Jamova 39, 1000 Ljubljana, Slovenia

* Author for correspondence (e-mail: janko.kos{at}ffa.uni-lj.si)

Accepted 19 May 2008

Cathepsin X is a lysosomal cysteine protease exhibiting carboxypeptidase activity. Its expression is high in the cells of immune system and its function has been related to the processes of inflammatory and immune responses. It regulates processes such as adhesion, T lymphocyte activation and phagocytosis through its interaction with β2 integrins. To investigate the role of cathepsin X in the migration of T lymphocytes, Jurkat T lymphocytes were stably transfected with a pcDNA3 expression vector containing cathepsin X cDNA. The cathepsin-X-overexpressing T lymphocytes exhibited polarised migration-associated morphology, enhanced migration on 2D and 3D models using intercellular adhesion molecule 1 (ICAM1)- and Matrigel-coated surfaces, and increased homotypic aggregation. The increased invasiveness of cathepsin-X-overexpressing cells does not involve proteolytic degradation of extracellular matrix. Confocal microscopy showed that the active mature form of cathepsin X was colocalised in migrating cells together with lymphocyte-function-associated antigen 1 (LFA-1). The colocalisation was particularly evident at the trailing edge protrusion, the uropod, that has an important role in T lymphocyte migration and cell-cell interactions. We propose that cathepsin X causes cytoskeletal rearrangements and stimulates migration of T lymphocytes by modulating the activity of the β2 integrin receptor LFA-1.

Key words: Cathepsin X, T lymphocytes, Integrins, Migration, Invasion


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