First published online September 18, 2007
Journal of Cell Science 120, 1805e (2007)
© The Company of Biologists Limited
Transglutaminase – crosstalking crosslinker
Cell-surface tissue transglutaminase (tTG) is a protein-crosslinking enzyme and an integrin-binding co-receptor for fibronectin in the extracellular matrix. Consequently, its precise regulation may be crucial to cell-matrix adhesion and adhesion signalling. On p. 3188, Alexey Belkin and co-workers reveal a new way in which cell-surface tTG is regulated – namely, through internalization and lysosomal degradation. The authors show that downregulation of cell-surface tTG depends on constitutive endocytosis and that efficient internalization of tTG involves clathrin- and caveolin-dependent pathways. They report that tTG interacts in vitro and in vivo with low-density-lipoprotein (LDL)-receptor-related protein 1 (LRP1) and that LRP1 is needed for endocytosis of tTG. Finally, they show that cell-surface levels of tTG are higher in LRP1-deficient cells and in cells where endosome/lysosome function is blocked. This change in tTG regulation, they report, increases cell adhesion and matrix crosslinking. Their results thus reveal a new mechanism for regulating cell-surface tTG, as well as establishing a key link between adhesion and endocytosis.
Related articles in JCS:
- Cell-surface transglutaminase undergoes internalization and lysosomal degradation: an essential role for LRP1
- Evgeny A. Zemskov, Irina Mikhailenko, Dudley K. Strickland, and Alexey M. Belkin
JCS 2007 120: 3188-3199.
[Abstract]
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