title: Neurotrophic signalling pathway triggered by prosaposin in PC12 cells occurs through lipid rafts.
abstract: Prosaposin is a neurotrophic factor that has been demonstrated to mediate trophic signalling events in different cell types; it distributes to surface membranes of neural cells and also exists as a secreted protein in different body fluids. Prosaposin was demonstrated to form tightly bound complexes with a variety of gangliosides, and a functional role has been suggested for ganglioside-prosaposin complexes. In this work, we provide evidence that exogenous prosaposin triggers a signal cascade after binding to its target molecules on lipid rafts of pheochromocytoma PC12 cell plasma membranes, as revealed by scanning confocal microscopy and linear sucrose gradient analysis. In these cells, prosaposin is able to induce extracellular signal-regulated kinase phosphorylation, sphingosine kinase activation, and consequent cell death prevention, acting through lipid rafts. These findings point to the role of lipid rafts in the prosaposin-triggered signalling pathway, thus supporting a role for this factor as a new component of the multimolecular signalling complex involved in the neurotrophic response.
authors.affiliation: Dipartimento di Medicina Sperimentale, Sapienza University, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Sorice
authors.forename: Sabrina
authors.initials: S
authors.lastname: Molinari
authors.forename: Luisa
authors.initials: L
authors.lastname: Di Marzio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mattei
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tasciotti
authors.forename: Laura
authors.initials: L
authors.lastname: Ciarlo
authors.forename: Masao
authors.initials: M
authors.lastname: Hiraiwa
authors.forename: Tina
authors.initials: T
authors.lastname: Garofalo
authors.forename: Roberta
authors.initials: R
authors.lastname: Misasi