Detection of p75NTR trimers: Implications for receptor stoichiometry and activation

• Autores: Anastasia Gonzalez, Agustin; Barker, Phillip A.; Chao, Moses V.; Hempstead, Barbara L.
• Año de publicación: 2015
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: P75NTR; PRONGF; SIGNALING UNIT; STOICHIOMETRY; TNF RECEPTOR; TRIMERIZATION
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

The p75 neurotrophin receptor (p75NTR) is a multifunctional receptor that participates in many critical processes in the nervous system, ranging from apoptosis to synaptic plasticity and morphological events. It is a member of the tumor necrosis factor receptor (TNFR) superfamily, whose members undergo trimeric oligomerization. Interestingly, p75NTR interacts with dimeric ligands (i.e., proneurotro-phins or mature neurotrophins), but several of the intracellular adaptors that mediate p75NTR signaling are trimeric (i.e., TNFR-associated factor 6 or TRAF6). Consequently, the active receptor signaling unit remains uncertain. To identify the functional receptor complex, we evaluated its oligomerization in vitro and in mice brain tissues using a combination of biochemical techniques. We found that the most abundant homotypic arrangement for p75NTR is a trimer and that monomers and trimers coexist at the cell surface. Interestingly, trimers are not required for ligand-independent or ligand-dependent p75NTR activation in a growth cone retraction functional assay. However, monomers are capable of inducing acute morphological effects in neurons. We propose that p75NTR activation is regulated by its oligomerization status and its levels of expression. These results indicate that the oligomeric state of p75NTR confers differential responses and offers an explanation for the diverse and contradictory actions of this receptor in the nervous system.
Fil: Anastasia Gonzalez, Agustin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Cornell University; Estados Unidos
Fil: Barker, Phillip A.. McGill University; Canadá
Fil: Chao, Moses V.. University Of New York. School Of Medicine; Estados Unidos
Fil: Hempstead, Barbara L.. Cornell University; Estados Unidos