Identification and Characterization of the Integrin alpha(2)beta(1) Binding Motif in Chondroadherin Mediating Cell Attachment

Lisbet Haglund, Viveka Tillgren, Laura Addis, Christina Wenglén, Anneliese Recklies, Dick Heinegård

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

28 Citeringar (SciVal)

Sammanfattning

Chondroadherin is a leucine-rich repeat protein known to mediate adhesion of isolated cells via the integrin alpha(2)beta(1) and to interact with collagen. In this work, we show that cell adhesion to chondroadherin leads to activation of MAPKs but does not result in cell spreading and division. This is in contrast to the spreading and dividing of cells grown on collagen, although the binding is mediated via the same alpha(2)beta(1) receptor. We identified a cell binding motif, CQLRGLRRWLEAK(318) by mass spectrometry after protease digestion of chondroadherin. Cells adhering to the synthetic peptide CQLRGLRRWLEAK(318) remained round, as was observed when they bound to the intact protein. The peptide added in solution was able to inhibit cell adhesion to the intact protein in a dose-dependent manner and was also verified to bind to the alpha(2)beta(1) integrin. A cyclic peptide, CQLRGLRRWLEAKASRPDATC(326), mimicking the structural constraints of this sequence in the intact protein, showed similar efficiency in inhibiting binding to chondroadherin. The unique peptide motif responsible for cellular binding is primarily located in the octamer sequence LRRWLEAK(318). Binding of cells to the active peptide or to chondroadherin immobilized on cell culture plates rapidly induces intracellular signaling (i.e. ERK phosphorylation). Thus, chondroadherin interaction with cells may be central for maintaining the adult chondrocyte phenotype and cartilage homeostasis. The peptides, particularly the more stable cyclic peptide, open new opportunities to modulate cell behavior in situations of tissue pathology.
Originalspråkengelska
Sidor (från-till)3925-3934
TidskriftJournal of Biological Chemistry
Volym286
Utgåva5
DOI
StatusPublished - 2011

Bibliografisk information

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Connective Tissue Biology (013230151)

Ämnesklassifikation (UKÄ)

  • Reumatologi och inflammation

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