TY - JOUR TI - The association of p75NTR and co-receptors in hippocampal neurons and astrocytes DO - https://doi.org/doi:10.7282/T3QR501J PY - 2015 AB - Neurons in the hippocampus are dependent on neurotrophins for survival. Upon injury, proneurotrophins cause hippocampal neurons to undergo apoptosis. These two distinct effects can be mediated by the interaction of p75NTR with different co-receptors. Trk receptors typically signal for survival and the signaling is enhanced in the presence of p75NTR. Apoptotic signaling through proneurotrophins is dependent on the presence of p75NTR and sortilin. The work in this thesis demonstrates that the association of p75NTR and TrkB, and the association of p75NTR with sortilin are both ligand dependent. The association of p75NTR and TrkB is dependent on internalization of the complex and TrkB activation . Sortilin and p75NTR associated both on the cell surface and in intracellular vesicles. Hippocampal astrocytes also express these receptors but do not signal for death upon proneurotophin treatment and are not dependent on mature neurotrophins for survival. This thesis demonstrates that the interaction of p75NTR and sortilin does not occur on hippocampal astrocytes. TrkB and p75NTR present on hippocampal astrocytes do not increase their association following treatment with BDNF. Taken together, the different responses between hippocampal neurons and astrocytes may be partially determined by limiting the interactions of p75NTR and co- receptors on astocytes. The data in this thesis demonstrate that the association of p75 with different co- receptors may determine the trafficking of these receptors through intracellular compartments, which is likely to influence intracellular signaling and the functional response of neurons and astrocytes to these factors. KW - Biology KW - Hippocampus (Brain) KW - Astrocytes LA - eng ER -