Biochemical interactions of the neuronal pentraxins - Neuronal pentraxin (NP) receptor binds to taipoxin and taipoxin-associated calcium-binding protein 49 via NP1 and NP2

Neuronal pentraxin 1 (NP1), neuronal pentraxin 2 (NP2), and neuronal pentra xin receptor (NPR) are members of a new family of proteins identified throu gh interaction with a presynaptic snake venom toxin taipoxin. We have propo sed that these three neuronal pentraxins represent a novel neuronal uptake pathway that may function during synapse formation and remodeling. We have investigated the mutual interactions of these proteins by characterizing th eir enrichment on taipoxin affinity columns; by expressing NP1, NP2, and NP R singly and together in Chinese hamster ovary cells; and by generating mic e that fail to express NP1. NP1 and NP2 are secreted, exist as higher order multimers (probably pentamers), and interact with taipoxin and taipoxin-as sociated calcium-binding protein 49 (TCBP49). NPR is expressed on the cell membrane and does not bind taipoxin or TCBP49 by itself, but it can form he teropentamers with NP1 and NP2 that can be released from cell membranes. Th is is the first demonstration of heteromultimerization of pentraxins and re lease of a pentraxin complex by proteolysis, These processes are likely to directly effect the localization and function of neuronal pentraxins in neu ronal uptake or synapse formation and remodeling.