p75 neurotrophin receptor and sortilin complex (p75NTR/sortilin complex)

The **p75 neurotrophin receptor (p75NTR) and sortilin complex** is a heteromeric receptor assembly crucial for proneurotrophin-mediated signaling in the nervous system[1][3][5]. p75NTR is a type I transmembrane receptor belonging to the tumor necrosis factor receptor superfamily; sortilin is a member of the Vps10p domain receptor family which functions as a sorting receptor and coreceptor[2][4]. When immature proneurotrophins (such as proNGF, proBDNF, or proNT-3) are present, their pro-domain binds to sortilin, while the mature domain binds to p75NTR, forming a ternary signaling complex. This complex is distinct in its ability to transduce cell death (apoptosis) signals, contrasting with the survival-promoting effects seen when mature neurotrophins bind to p75NTR and Trk co-receptors[1][5]. The complex plays key roles in neuronal development, synaptic modulation, injury response, and immune signaling, but is also implicated in pathological processes such as neurodegeneration and tumor biology. Targeting this complex poses both promise and risk as a therapeutic strategy due to its dual roles in neuronal survival and apoptosis[5].

Other names

p75 neurotrophin receptor and sortilin heteromeric complexLow-affinity nerve growth factor receptor/sortilin complexNGFR/sortilin complexCD271/sortilin complex

Modulation of neurotrophin binding (pro-neurotrophin binds sortilin, mature neurotrophin binds p75NTR); Promotion of apoptosis via proneurotrophin-induced activation; Regulation of intramembrane proteolysis and receptor shedding (leading to downstream signaling); Competitive inhibition of ligand binding (for potential inhibitors).