Milward Elizabeth, Kim Kee Jun, Szklarczyk Arek, Nguyen Thien, Melli Giorgia, Nayak Mamatha, Deshpande Deepa, Fitzsimmons Chantel, Hoke Ahmet, Kerr Douglas, Griffin John W, Calabresi Peter A, Conant Katherine
School of Biomedical Sciences, The University of Newcastle and the Hunter Medical Research Institute, Callaghan, New South Wales 2308, Australia.
J Neuroimmunol. 2008 Jan;193(1-2):140-8. doi: 10.1016/j.jneuroim.2007.11.001. Epub 2007 Dec 11.
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.
衍生髓磷脂相关糖蛋白（dMAG）由跨膜髓磷脂相关糖蛋白（MAG）经蛋白水解产生，可抑制轴突生长。我们测试了某些在炎症性和脱髓鞘疾病中水平升高的基质金属蛋白酶（MMP）切割MAG的能力。我们发现MMP-2、MMP-7和MMP-9可切割重组人MAG，而MMP-1则不能。MMP-7在Leu 509处切割，该位点恰好在跨膜结构域的远端，在较小程度上也在Met 234处切割。我们还表明，MMP-7可切割CHO细胞外表面表达的MAG，释放出的片段在长达48小时或更长时间内积聚在培养基中，并且能够抑制背根神经节（DRG）神经元的生长。我们得出结论，MMP可能既有破坏MAG依赖的轴突-神经胶质细胞通讯的潜力，又有产生可抑制神经突生长的生物活性片段的潜力。
