title: Palmitoylation at Cys574 is essential for MT1-MMP to promote cell migration.
abstract: MT1-MMP is a type I transmembrane proteinase that promotes cell migration and invasion. Here, we report that MT1-MMP is palmitoylated at Cys574 in the cytoplasmic domain, and this lipid modification is critical for its promotion of cell migration and clathrin-mediated internalization. The palmitoylation-defective mutant (C574A) failed to promote cell migration and was not internalized through clathrin pathway like wild-type, but it was internalized through the caveolae pathway. Reintroducing a cysteine at different positions in the cytoplasmic tail of the C574A mutant revealed that the position of the palmitoylated cysteine relative to LLY573, a motif that interacts with mu2 subunit of adaptor protein 2, is critical for the cell motility-promoting activity of MT1-MMP and its clathrin-mediated internalization. Taken together, palmitoylation of MT1-MMP is one of the key posttranslational modifications that determines MT1-MMP-dependent cell migration.
authors.affiliation: Department of Matrix Biology, Kennedy Institute of Rheumatology Division, Imperial College London, London, UK.
authors.forename: Narayanapanicker
authors.initials: N
authors.lastname: Anilkumar
authors.forename: Takamasa
authors.initials: T
authors.lastname: Uekita
authors.forename: John R
authors.initials: JR
authors.lastname: Couchman
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nagase
authors.forename: Motoharu
authors.initials: M
authors.lastname: Seiki
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Itoh
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D021941:Caveolae / Q000502:physiology; D002465:Cell Movement; D002522:Chlorocebus aethiops; D002966:Clathrin / Q000502:physiology; D006224:Cricetinae; D003545:Cysteine; D053511:Matrix Metalloproteinase 14; D020782:Matrix Metalloproteinases / Q000737:chemistry / Q000502:physiology*; D053504:Matrix Metalloproteinases, Membrane-Associated; D051379:Mice; D019308:Palmitic Acid / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
chemical_list: D002966:Clathrin; C507096:Mmp14 protein, mouse; D019308:Palmitic Acid; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D053511:Matrix Metalloproteinase 14; D003545:Cysteine