Shedding of the p75NTR neurotrophin receptor is modulated by lipid rafts

Protein ectodomain shedding is the proteolytic release of the extracellular domain of membrane-bound proteins. Neurotrophin receptor p75NTR is known to be affected by shedding. The present work provides evidence, in rat brain synaptosomes, that p75NTR is present in detergent-resistant membranes (DRM), also known as lipid rafts, only in its full-length form. Disrupting the integrity of lipid rafts causes solubilization of p75NTR after detergent treatment and enhancement of the shedding. Analyses of the enzymes described as being responsible for p75NTR shedding, i.e. tumor necrosis factor α convertase (TACE) and presenilin-1 (PS1), revealed that TACE is absent in DRM, while variable proportions of the C-terminal and N-terminal fragments of PS1 are found. In summary, our results point to a role of lipid rafts in the modulation of the shedding of the p75NTR receptor.