Ectodomain shedding of human Nogo-66 receptor homologue-1 by zinc metalloproteinases

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• 作者：Walmsley ; Adrian R. ; Mir ; Anis K. ; Frentzel ; Stefan
• 关键词：Ectodomain shedding ; Neurite outgrowth inhibition ; Nogo-66 receptor homologue-1 ; Zinc metalloproteinase
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2005
• 出版时间：February 4, 2005
• 年：2005
• 卷：327
• 期：1
• 页码：112-116
• 全文大小：259 K

文摘

The Nogo-66 receptor (NgR) plays a pivotal role in the inhibition of neuroregeneration as the receptor for multiple neurite outgrowth inhibitors such as Nogo-A. We have previously shown that NgR undergoes zinc metalloproteinase-mediated ectodomain shedding in neuroblastoma cells. Here, we demonstrate that the NgR-related protein NgR homologue-1 is released from neuroblastoma cells as a full-length ectodomain (NgRH1-ecto) and an N-terminal fragment (NTF-NgRH1) containing the leucine-rich repeat region of the protein. Inhibitors of the major protease classes failed to block the release of NgRH1-ecto, suggesting that this occurs via a protease-independent mechanism, presumably by a phospholipase-like enzyme. The release of NTF-NgRH1 was blocked by a hydroxamate-based zinc metalloproteinase inhibitor and tissue inhibitor of metalloproteinases-2 and -3, but not -1, implicating the involvement of membrane-type matrix metalloproteinases in this process. Our findings thus highlight the parallels between the ectodomain shedding of NgRH1 and that previously described for NgR.