Association of p75(NTR) and α9β1 integrin modulates NGF-dependent cellular responses.
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 p75(NTR) 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 p75(NTR) on the cellular membrane by selective immunoprecipitation experiments. The presence of the α9/p75(NTR) complex increases NGF-dependent cell adhesion, proliferation and migration. Other integrin subunits including β1 were not found in complex with p75(NTR). FRET analysis indicated that p75(NTR) 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 p75(NTR). α9/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.
CoE Department of Bioengineering, Temple University, Philadelphia, PA, USA.
Erin M
EM
Ventresca
CoE Department of Bioengineering, Temple University, Philadelphia, PA, USA.
Shimon
S
Lecht
CoE Department of Bioengineering, Temple University, Philadelphia, PA, USA.
Piotr
P
Jakubowski
CoE Department of Bioengineering, Temple University, Philadelphia, PA, USA.
Rachel A
RA
Chiaverelli
Department of Neurosurgery, Temple University Hospital, Philadelphia, PA, USA.
Michael
M
Weaver
Department of Medicine and Pathology, Stanley Scott Cancer Center, Louisiana State University, New Orleans, LA, USA.
Luis
L
Del Valle
School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
Keren
K
Ettinger
School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
Galit
G
Gincberg
School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
Avi
A
Priel
The Shraga Segal Department of Microbiology, Immunology and Genetics, The Faculty of Health Science, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Alex
A
Braiman
CoE Department of Bioengineering, Temple University, Philadelphia, PA, USA; School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
Philip
P
Lazarovici
CoE Department of Bioengineering, Temple University, Philadelphia, PA, USA.
Peter I
PI
Lelkes
CoE Department of Bioengineering, Temple University, Philadelphia, PA, USA. Electronic address: cmarcink@temple.edu.
Cezary
C
Marcinkiewicz
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D031541:Fluorescence Resonance Energy Transfer; D057809:HEK293 Cells; D006801:Humans; D007150:Immunohistochemistry; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020932:Nerve Growth Factor / Q000302:isolation & purification / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051419:Paxillin / Q000378:metabolism; D011485:Protein Binding; D020917:Receptor, trkA / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D016023:Integrins; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D051419:Paxillin; D017475:Receptors, Nerve Growth Factor; D019010:Vascular Cell Adhesion Molecule-1; C113256:integrin alpha 9 beta 1; D020932:Nerve Growth Factor; D020917:Receptor, trkA; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
Cell adhesion; Cell signaling; Integrin α9β1; Receptor complex; p75(NTR)