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FHL2 interacts with both ADAM‐17 and the cytoskeleton and regulates ADAM‐17 localization and activity
Author(s) -
Canault Matthias,
Tellier Edwige,
Bonardo Bernadette,
Mas Eric,
Aumailley Monique,
JuhanVague Irène,
Nalbone Gilles,
Peiretti Franck
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20671
Subject(s) - ectodomain , microbiology and biotechnology , actin cytoskeleton , disintegrin , colocalization , biology , cytoskeleton , actin , metalloproteinase , cell , biochemistry , receptor , matrix metalloproteinase
ADAM‐17 is a metalloprotease‐disintegrin responsible for the ectodomain shedding of several transmembrane proteins. Using the yeast two‐hybrid system, we showed that ADAM‐17 interacts with the Four and Half LIM domain 2 protein (FHL2), a LIM domain protein that is involved in multiple protein‐protein interaction. We demonstrated that this interaction involved the amino‐acid sequence of ADAM‐17 from position 721 to739. In the cardiomyoblast cells H9C2, ADAM‐17 and FHL2 colocalize with the actin‐based cytoskeleton and we showed that FHL2 binds both ADAM‐17 and the actin‐based cytoskeleton. We found that mainly the mature form of ADAM‐17 associates with the cytoskeleton, although the maturation of ADAM‐17 by furin is not necessary for its binding to the cytoskeleton. Interestingly, less ADAM‐17 was detected at the surface of wild‐type mouse macrophages compared to FHL2 deficient macrophages. However, wild‐type cells have a higher ability to release ADAM‐17 substrates under PMA stimulation. Altogether, these results demonstrate a physical and functional interaction between ADAM‐17 and FHL2 that implies that FHL2 has a role in the regulation of ADAM‐17. J. Cell. Physiol. 208: 363–372, 2006. © 2006 Wiley‐Liss, Inc.