The membrane-anchored metalloproteinase regulator RECK stabilizes focal adhesions and anterior-posterior polarity in fibroblasts.
Accumulating evidence indicates that Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a membrane-anchored matrix metalloproteinase regulator, plays crucial roles in mammalian development and tumor suppression. Its mechanisms of action at the single cell level, however, remain largely unknown. In mouse fibroblasts, RECK is abundant around the perinuclear region, membrane ruffles and cell surface. Cells lacking Reck show decreased spreading, ambiguous anterior-posterior (AP) polarity, and increased speed and decreased directional persistence in migration; these characteristics are also found in transformed fibroblasts and fibrosarcoma cells with low RECK expression. RECK-deficient cells fail to form discrete focal adhesions, have increased levels of GTP-bound Rac1 and Cdc42, and a marked decrease in the level of detyrosinated tubulin, a hallmark of stabilized microtubules. RECK-deficient cells also show elevated gelatinolytic activity and decreased fibronectin fibrils. The phenotype of RECK-deficient cells is largely suppressed when the cells are plated on fibronectin-coated substrates. These findings suggest that RECK regulates pericellular extracellular matrix degradation, thereby allowing the cells to form proper cell-substrate adhesions and to maintain AP polarity during migration; this mechanism is compromised in malignant cells.
Morioka
Y
Y
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Yoshida-Konoe-cho, Sakyo-ku, Kyoto, Japan.
Monypenny
J
J
Matsuzaki
T
T
Shi
S
S
Alexander
D B
DB
Kitayama
H
H
Noda
M
M
D000199:Actins / Q000502:physiology; D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D002478:Cells, Cultured; D024042:Collagen Type I / Q000502:physiology; D005347:Fibroblasts / Q000166:cytology; D005353:Fibronectins / Q000502:physiology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000502:physiology; D022001:Focal Adhesions; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins / Q000032:analysis / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D009479:Neuropeptides / Q000502:physiology; D012509:Sarcoma / Q000473:pathology; D020764:cdc42 GTP-Binding Protein / Q000502:physiology; D020744:rac GTP-Binding Proteins / Q000502:physiology; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins / Q000502:physiology
D000199:Actins; D024042:Collagen Type I; D005353:Fibronectins; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D009479:Neuropeptides; C484602:Rac1 protein, mouse; C492025:Reck protein, mouse; D051416:Focal Adhesion Protein-Tyrosine Kinases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins