S.Terawaki
et al.
(2015).
MT1-MMP recognition by ERM proteins and its implication in CD44 shedding.
Genes Cells,
20,
847-859.
PubMed id: 26289026
DOI: 10.1111/gtc.12276
Membrane type 1-matrix metalloproteinase (MT1-MMP) is a key enzyme involved in
tumor cell invasion by shedding their cell-surface receptor CD44 anchored with
F-actin through ezrin/radixin/moesin (ERM) proteins. We found the cytoplasmic
tail of MT1-MMP directly binds the FERM domain of radixin, suggesting
F-actin-based recruitment of MT1-MMP to CD44 for invasion. Our crystal structure
shows that the central region of the MT1-MMP cytoplasmic tail binds subdomain A
of the FERM domain, and makes an antiparallel β-β interaction with
β2A-strand. This binding mode is distinct from the previously determined
binding mode of CD44 to subdomain C. We showed that radixin simultaneously binds
both MT1-MMP and CD44, indicating ERM protein-mediated colocalization of MT1-MMP
and its substrate CD44 and anchoring to F-actin. Our study implies that ERM
proteins contribute toward accelerated CD44 shedding by MT1-MMP through ERM
protein-mediated interactions between their cytoplasmic tails.
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