The third type III module of human fibronectin mediates cell adhesion and migration.
Fibronectin (FN) is a major extracellular matrix protein involved in various biological events. This study demonstrated that the third FN type III repeat (FnIII3) and several fragments containing the repeat promote cell spreading and migration of human dermal fibroblasts (HDFs), whereas the fourth repeat (FnIII4) did not. A variety of cell types also spread on FnIII3 in a cell-type-specific manner, but not on FnIII4. Immunofluorescence assays revealed that FnIII3 induced the organization of focal contacts and stress fibres in HDFs. Cyclic [RGDFV] peptides with a D-Phe residue, which are selective inhibitors of cell adhesion to vitronectin, inhibited HDF spreading on FnIII3 equally with GRGDS, indicating little involvement of alphaV-integrins in FnIII3 spreading. An anti-beta1 integrin mAb inhibited cell spreading on FnIII3 and FN. To our knowledge, this is the first demonstration that a novel domain of FnIII3 functions in cell spreading and migration through an interaction with unresolved beta1 integrin(s) in an RGD-dependent manner.
Obara
Masanobu
M
Laboratory of Developmental Biology, Department of Biological Science, Graduate School of Science, Hiroshima University, 1-3-1 Kagamiyama, Higashihiroshima, Hiroshima 739-8526, Japan. msobara@hiroshima-u.ac.jp
Sakuma
Tetsushi
T
Fujikawa
Kazuyuki
K
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002448:Cell Adhesion; D002460:Cell Line; D002465:Cell Movement; D020405:Dermis / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology; D005353:Fibronectins / Q000737:chemistry / Q000502:physiology; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics
D000970:Antineoplastic Agents; D005353:Fibronectins; D039564:Integrin alphaV; D019012:Integrin beta1; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C047981:arginyl-glycyl-aspartic acid