The mesenchymal alpha11beta1 integrin attenuates PDGF-BB-stimulated chemotaxis of embryonic fibroblasts on collagens.
alpha11beta1 constitutes the most recent addition to the integrin family and has been shown to display a binding preference for interstitial collagens found in mesenchymal tissues. We have previously observed that when alpha11beta1 integrin is expressed in cells lacking endogenous collagen receptors, it can mediate PDGF-BB-dependent chemotaxis on collagen I in vitro. To determine in which cells PDGF and alpha11beta1 might cooperate in regulating cell migration in vivo, we studied in detail the expression and distribution of alpha11 integrin chain in mouse embryos and tested the ability of PDGF isoforms to stimulate the alpha11beta1-mediated cell migration of embryonic fibroblasts. Full-length mouse alpha11 cDNA was sequenced and antibodies were raised to deduced alpha11 integrin amino acid sequence. In the embryonic mouse head, alpha11 protein and RNA were localized to ectomesenchymally derived cells. In the periodontal ligament, alpha11beta1 was expressed as the only detectable collagen-binding integrin, and alpha11beta1 is thus a major receptor for cell migration and matrix organization in this cell population. In the remainder of the embryo, the alpha11 chain was expressed in a subset of mesenchymal cells including tendon/ligament fibroblasts, perichondrial cells, and intestinal villi fibroblasts. Most of the alpha11-expressing cells also expressed the alpha2 integrin chain, but no detectable overlap was found with the alpha1 integrin chain. In cells expressing multiple collagen receptors, these might function to promote a more stable cell adhesion and render the cells more resistant to chemotactic stimuli. Wild-type embryonic fibroblasts activated mainly the PDGF beta receptor in response to PDGF-BB and migrated on collagens I, II, III, IV, V, and XI in response to PDGF-BB in vitro, whereas mutant fibroblasts that lacked alpha11beta1 in their collagen receptor repertoire showed a stronger chemotactic response on collagens when stimulated with PDGF-BB. In the cellular context of embryonic fibroblasts, alpha11beta1 is thus anti-migratory. We speculate that the PDGF BB-dependent cell migration of mesenchymal cells is tightly regulated by the collagen receptor repertoire, and disturbances of this repertoire might lead to unregulated cell migration that could affect normal embryonic development and tissue structure.
Popova
Svetlana N
SN
Department of Medical Biochemistry and Microbiology, Biomedical Center, Uppsala, Sweden.
Rodriguez-Sánchez
Belén
B
Lidén
Asa
A
Betsholtz
Christer
C
Van Den Bos
Theo
T
Gullberg
Donald
D
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D000077214:Becaplermin; D015152:Blotting, Northern; D015153:Blotting, Western; D002465:Cell Movement / Q000502:physiology; D002633:Chemotaxis / Q000502:physiology*; D024042:Collagen Type I / Q000378:metabolism*; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004586:Electrophoresis; D005347:Fibroblasts; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D039001:Integrin alpha Chains / Q000235:genetics*; D016023:Integrins / Q000235:genetics / Q000378:metabolism*; D051379:Mice / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011233:Precipitin Tests; D020574:Proto-Oncogene Proteins c-sis; D038981:Receptors, Collagen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D024042:Collagen Type I; D017931:DNA Primers; D018076:DNA, Complementary; D039001:Integrin alpha Chains; D016023:Integrins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D038981:Receptors, Collagen; C467800:integrin alpha11beta1; D000077214:Becaplermin