Association of p75(NTR) and $\alpha$9$\beta$1 integrin modulates NGF-dependent cellular responses.

תקציר:

Direct interaction of $\alpha$9$\beta$1 integrin with nerve growth factor (NGF) has been previously reported to induce pro-proliferative and pro-survival activities of non-neuronal cells. We investigated participation of p75(NTR) in $\alpha$9$\beta$1 integrin-dependent cellular response to NGF stimulation. Using selective transfection of glioma cell lines with these receptors, we showed a strong, cation-independent association of $\alpha$9 integrin subunit with p75(NTR) on the cellular membrane by selective immunoprecipitation experiments. The presence of the $\alpha$9/p75(NTR) complex increases NGF-dependent cell adhesion, proliferation and migration. Other integrin subunits including $\beta$1 were not found in complex with p75(NTR). FRET analysis indicated that p75(NTR) and $\alpha$9 integrin subunit are not closely associated through their cytoplasmic domains, most probably because of the molecular interference with other cytoplasmic proteins such as paxillin. Interaction of $\alpha$9$\beta$1 integrin with another ligand, VCAM-1 was not modulated by the p75(NTR). $\alpha$9/p75(NTR) complex elevated NGF-dependent activation of MAPK Erk1/2 arty for integrin that may create active complexes with other types of receptors belonging to the TNF superfamily.