Lipid rafts identified as locations of ectodomain shedding mediated by Meltrin β/ADAM19
Article first published online: 4 MAR 2004
Journal of Neurochemistry
Volume 89, Issue 1, pages 119–123, April 2004
How to Cite
Wakatsuki, S., Kurisaki, T. and Sehara-Fujisawa, A. (2004), Lipid rafts identified as locations of ectodomain shedding mediated by Meltrin β/ADAM19. Journal of Neurochemistry, 89: 119–123. doi: 10.1046/j.1471-4159.2003.02303.x
- Issue published online: 10 MAR 2004
- Article first published online: 4 MAR 2004
- Received November 10, 2003; revised manuscript received November 25, 2003; accepted November 26, 2003.
- ectodomain shedding;
- lipid rafts;
Meltrin β (Mel β, also called ADAM19) is a member of the ADAM (adisintegrin and metalloprotease) family, which are membrane-anchored glycoproteins that play crucial roles in various biological processes. Many intercellular signaling molecules are membrane-anchored proteins, which are proteolytically processed after becoming membrane-bound, to liberate their extracellular domains (ectodomain shedding). Genetic and biochemical studies have shown that some ADAMs participate in these events. We found previously that Mel β can cleave the extracellular region of the membrane-anchored β-exon-containing Neuregulin-1 (NRG β1) protein, which is one of the main ligands for the neural ErbB receptor. Mel β-deficient mice showed developmental defects in the nervous system. These observations raise the possibility that the NRG ectodomain shedding mediated by Mel β is closely related to the neural development. Here we show that Mel β-mediated ectodomain shedding of NRG β1 takes place in the lipid rafts of neurons. The lipid rafts localization of Mel β requires its membrane-anchoring region, and NRG β1 ectodomain shedding is not enhanced if Mel β cannot reach the lipid rafts. These results indicate that localization of Mel β in lipid rafts is critical for its ectodomain shedding.