Association of p75NTR and α9β1 integrin modulates NGF-dependent cellular responses

Erin M. Ventresca, Shimon Lecht, Piotr Jakubowski, Rachel A. Chiaverelli, Michael Weaver, Luis Del Valle, Keren Ettinger, Galit Gincberg, Avi Priel, Alex Braiman, Philip Lazarovici, Peter I. Lelkes, Cezary Marcinkiewicz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Direct interaction of α9β1 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 p75NTR in α9β1 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 α9 integrin subunit with p75NTR on the cellular membrane by selective immunoprecipitation experiments. The presence of the α9/p75NTR complex increases NGF-dependent cell adhesion, proliferation and migration. Other integrin subunits including β1 were not found in complex with p75NTR. FRET analysis indicated that p75NTR and α9 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 α9β1 integrin with another ligand, VCAM-1 was not modulated by the p75NTR. α9/p75NTR 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.

Original languageAmerican English
Pages (from-to)1225-1236
Number of pages12
JournalCellular Signalling
Issue number6
StatePublished - 1 Jun 2015

Bibliographical note

Funding Information:
We are grateful to Dr. Dean Sheppard for generously providing many of the reagents for investigating α9β1 integrin and for his valuable comments during the preparation of the manuscript. This work was supported by the National Institutes of Health National Cancer Institute [grant number R01CA133262 to C.M. ]; grant from The Louis & Bessie Stein Family Foundation (to P.I.L. and P.L.); David R. Bloom Center of Pharmacy and Dr. Adolf and Klara Brettler Center for Research in Molecular Pharmacology and Therapeutics at The Hebrew University of Jerusalem, Israel (to P.L.).

Publisher Copyright:
© 2015 Elsevier Inc.


  • Cell adhesion
  • Cell signaling
  • Integrin α9β1
  • P75
  • Receptor complex


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