Cleavage of myelin associated glycoprotein by matrix metalloproteinases

Elizabeth Milward, Kee Jun Kim, Arek Szklarczyk, Thien Nguyen, Giorgia Melli, Mamatha Nayak, Deepa Deshpande, Chantel Fitzsimmons, Ahmet Hoke, Douglas Kerr, John W. Griffin, Peter A. Calabresi, Katherine Conant

Research output: Contribution to journalArticlepeer-review

Abstract

Derivative myelin associated glycoprotein (dMAG) results from proteolysis of transmembrane MAG and can inhibit axonal growth. We have tested the ability of certain matrix metalloproteinases (MMPs) elevated with inflammatory and demyelinating diseases to cleave MAG. We show MMP-2, MMP-7 and MMP-9, but not MMP-1, cleave recombinant human MAG. Cleavage by MMP-7 occurs at Leu 509, just distal to the transmembrane domain and, to a lesser extent, at Met 234. We also show that MMP-7 cleaves MAG expressed on the external surface of CHO cells, releasing fragments that accumulate in the medium over periods of up to 48 h or more and that are able to inhibit outgrowth by dorsal root ganglion (DRG) neurons. We conclude that MMPs may have the potential both to disrupt MAG dependent axon-glia communication and to generate bioactive fragments that can inhibit neurite growth.

Original languageEnglish (US)
Pages (from-to)140-148
Number of pages9
JournalJournal of Neuroimmunology
Volume193
Issue number1-2
DOIs
StatePublished - Jan 1 2008

Keywords

  • MAG
  • MMP
  • Multiple sclerosis
  • Myelin
  • Proteinase

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Neurology
  • Clinical Neurology

Fingerprint Dive into the research topics of 'Cleavage of myelin associated glycoprotein by matrix metalloproteinases'. Together they form a unique fingerprint.

Cite this