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

Haglund, Lisbet; Tillgren, Viveka LU ; Addis, Laura LU ; Wenglén, Christina LU ; Recklies, Anneliese and Heinegård, Dick LU (2011) In Journal of Biological Chemistry 286(5). p.3925-3934
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
286
issue
5
pages
3925 - 3934
publisher
ASBMB
external identifiers
  • wos:000286653200073
  • scopus:79952787377
ISSN
1083-351X
DOI
10.1074/jbc.M110.161141
language
English
LU publication?
yes
id
27fc1cf3-4a16-442b-86c6-c08b46246b6d (old id 1878000)
date added to LUP
2011-04-01 10:41:55
date last changed
2017-10-22 03:23:11
@article{27fc1cf3-4a16-442b-86c6-c08b46246b6d,
  abstract     = {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.},
  author       = {Haglund, Lisbet and Tillgren, Viveka and Addis, Laura and Wenglén, Christina and Recklies, Anneliese and Heinegård, Dick},
  issn         = {1083-351X},
  language     = {eng},
  number       = {5},
  pages        = {3925--3934},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Identification and Characterization of the Integrin alpha(2)beta(1) Binding Motif in Chondroadherin Mediating Cell Attachment},
  url          = {http://dx.doi.org/10.1074/jbc.M110.161141},
  volume       = {286},
  year         = {2011},
}