Mecham Robert P, Gibson Mark A
Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
School of Medical Sciences, University of Adelaide, Adelaide, South Australia 5005, Australia.
Matrix Biol. 2015 Sep;47:13-33. doi: 10.1016/j.matbio.2015.05.003. Epub 2015 May 8.
The microfibril-associated glycoproteins MAGP-1 and MAGP-2 are extracellular matrix proteins that interact with fibrillin to influence microfibril function. The two proteins are related through a 60 amino acid matrix-binding domain but their sequences differ outside of this region. A distinguishing feature of both proteins is their ability to interact with TGFβ family growth factors, Notch and Notch ligands, and multiple elastic fiber proteins. MAGP-2 can also interact with αvβ3 integrins via a RGD sequence that is not found in MAGP-1. Morpholino knockdown of MAGP-1 expression in zebrafish resulted in abnormal vessel wall architecture and altered vascular network formation. In the mouse, MAGP-1 deficiency had little effect on elastic fibers in blood vessels and lung but resulted in numerous unexpected phenotypes including bone abnormalities, hematopoietic changes, increased fat deposition, diabetes, impaired wound repair, and a bleeding diathesis. Inactivation of the gene for MAGP-2 in mice produced a neutropenia yet had minimal effects on bone or adipose homeostasis. Double knockouts had phenotypes characteristic of each individual knockout as well as several additional traits only seen when both genes are inactivated. A common mechanism underlying all of the traits associated with the knockout phenotypes is altered TGFβ signaling. This review summarizes our current understanding of the function of the MAGPs and discusses ideas related to their role in growth factor regulation.
微原纤维相关糖蛋白MAGP-1和MAGP-2是细胞外基质蛋白，它们与原纤蛋白相互作用以影响微原纤维的功能。这两种蛋白通过一个60个氨基酸的基质结合结构域相关联，但在该区域之外它们的序列不同。这两种蛋白的一个显著特征是它们能够与转化生长因子β（TGFβ）家族生长因子、Notch和Notch配体以及多种弹性纤维蛋白相互作用。MAGP-2还可以通过MAGP-1中不存在的RGD序列与αvβ3整合素相互作用。在斑马鱼中，通过吗啉代敲低MAGP-1的表达会导致血管壁结构异常和血管网络形成改变。在小鼠中，MAGP-1缺陷对血管和肺中的弹性纤维影响很小，但会导致许多意想不到的表型，包括骨骼异常、造血变化、脂肪沉积增加、糖尿病、伤口修复受损和出血倾向。在小鼠中使MAGP-2基因失活会导致中性粒细胞减少，但对骨骼或脂肪稳态的影响最小。双敲除具有每个单敲除的特征性表型以及一些仅在两个基因都失活时才出现的其他特征。与敲除表型相关的所有性状的一个共同潜在机制是TGFβ信号改变。本综述总结了我们目前对MAGP功能的理解，并讨论了与其在生长因子调节中的作用相关的观点。
