Association of p75(NTR) and ?9?1 integrin modulates NGF-dependent cellular responses.

ABSTRACT: Direct interaction of ?9?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 ?9?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 ?9 integrin subunit with p75(NTR) on the cellular membrane by selective immunoprecipitation experiments. The presence of the ?9/p75(NTR) complex increases NGF-dependent cell adhesion, proliferation and migration. Other integrin subunits including ?1 were not found in complex with p75(NTR). FRET analysis indicated that p75(NTR) and ?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 ?9?1 integrin with another ligand, VCAM-1 was not modulated by the p75(NTR). ?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.

SUBMITTER: Ventresca EM 

PROVIDER: S-EPMC4409011 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature