Cleavage of Myelin Associated Glycoprotein by Matrix Metalloproteinases

Overview

Journal J Neuroimmunol

Specialty Neurology

Date 2007 Dec 8

PMID 18063113

Citations 25

Authors

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

Affiliations

Soon will be listed here.

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.

Citing Articles

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