טכניון מכון טכנולוגי לישראל
הטכניון מכון טכנולוגי לישראל - בית הספר ללימודי מוסמכים  
M.Sc Thesis
M.Sc StudentAviram Rohtem
SubjectExploring the interactions between LOX and ADAMTS/L
proteins
DepartmentDepartment of Medicine
Supervisors Professor Peleg Hasson
Professor Emeritus Gera Neufeld
Full Thesis textFull thesis text - English Version


Abstract

Extra-cellular homeostasis is mediated by protein interactions that support tissue structure and cellular signaling. Lysyl oxidase (LOX) is a fundamental, secreted matrix modifying enzyme hence its controlled activity is critical for the regulation of extra-cellular matrix (ECM) formation and maintenance. Yet, although being a key regulator, understanding of LOX's activity remains partially unclear. A yeast 2-hybrid (Y2H) screen carried out to identify putative LOX interactors has demonstrated that it can complex with another ECM regulator - ADAMTSL-4.

In this study we provide further evidence for this interaction and extend it to additional ADAMTS/L family members. Likewise, we demonstrate that ADAMTS/L proteins could also interact with further members of the LOX family. The importance of the interactions between Lox and the ADAMTS/L proteins can be observed in Lox null mice embryos, where we observed reduced levels of Adamtsl-2. To determine whether reduced Adamtsl-2 expression is due to lack of Lox catalytic activity or because of the lack of protein mice were treated with BAPN, an inhibitor of LOX-family enzymatic activity. Our results indicate that Adamtsl-2 protein levels are reduced also in BAPN-treated animals demonstrating that Lox catalytic activity is essential for Adamtsl-2 stability. Additional observations suggest that not only are Adamtsl-2 levels reduced in Lox mutant embryos but also that it forms distinct complexes in the lack of active Lox.

Altogether, our results suggest that the interaction between LOX and ADAMTS/L proteins plays a significant role during ECM development and maintenance. We further propose that these interactions have an important role in the regulation of signaling pathways such as TGF-β.

Further research into the interactions between these two ECM-modifying protein families will allow a better understanding of the mechanisms by which the ECM regulates multiple cellular processes.