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 p75(NTR) is known to be affected by shedding. The present work provides evidence, in rat brain synaptosomes, that p75(NTR) 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 p75(NTR) after detergent treatment and enhancement of the shedding. Analyses of the enzymes described as being responsible for p75(NTR) shedding, i.e. tumor necrosis factor alpha 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 p75(NTR) receptor.
Gil
Carles
C
Departament de Bioquímica i Biologia Molecular and Institut de Neurociències, Edifici M, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Catalunya, Spain. carles.gil@uab.cat
Cubí
Roger
R
Aguilera
José
J
D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D000818:Animals; D002784:Cholesterol / Q000502:physiology; D003902:Detergents / Q000494:pharmacology; D006801:Humans; D021962:Membrane Microdomains / Q000502:physiology*; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D053764:Presenilin-1 / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*
D003902:Detergents; D053764:Presenilin-1; D020800:Receptor, Nerve Growth Factor; D002784:Cholesterol; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human; C000606464:Adam17 protein, rat