Cell Adhesion

Moving Fer for Less Adhesion

Science's STKE  20 Jun 2000:
Vol. 2000, Issue 37, pp. tw2
DOI: 10.1126/stke.2000.37.tw2

Cadherin and integrin are proteins that mediate cellular adhesion at sites of cell-cell contact (cadherin) or sites of contact with the extracellular matrix (integrins). Two papers describe how cadherin- and integrin-mediated cellular adhesion are coordinately regulated. Li et al. cloned the ligand, neurocan, for the cell-surface galactosyltransferase that is associated with N-cadherin. Treatment of retinal cells with either full-length neurocan or an NH2 fragment of neurocan inhibited cadherin- and integrin-mediated cell adhesion and neurite outgrowth and increased phosphorylation of β-catenin. The ability of neurocan to inhibit adhesion was dependent on the presence of the cell-surface galactosyltransferase. Arregui et al. disrupted cadherin- and integrin-mediated adhesion and neurite outgrowth with membrane-permeable peptides and found that the peptide mimicking the juxtamembrane domain of cadherin (JMP) caused the dissociation of the nonreceptor protein kinase Fer from the cadherin complex and its association with the integrin complex. The ability of JMP to inhibit integrin-mediated adhesion was dependent on the presence of N-cadherin and could be blocked with a Fer peptide that blocked the association of Fer with the integrin complex. Li et al. found that treatment of cells with neurocan also caused the release of Fer from the cadherin complex and association with the integrin complex. Thus, neurocan may be an endogenous ligand that promotes the cross-talk between cadherin and integrin complexes through relocalization of Fer.

Li, H., Leung, T.-C., Hoffman, S., Balsamo, J., and Lilien, J. (2000) Coordinate regulation of cadherin and integrin function by the chondroitin sulfate proteoglycan neurocan. J. Cell Biol. 149: 1275-1288. [Abstract] [Full Text]

Arregui, C., Pathre, P., Lilien, J., and Balsamo, J. (2000) The nonreceptor tyrosine kinase Fer mediates cross-talk between the N-cadherin and β1-integrins. J. Cell Biol. 149: 1263-1273. [Abstract] [Full Text]