Washington University in St. Louis

New Publication for Mecham Lab

Congratulations to Bob Mecham and colleague, Mark Gibson on their new publication in Matrix Biology.

Mecham, RP and Gibson, MA  (2015)  The Microfibril-Associated Glycoproteins (MAGPs) and the Microfibrillar Niche.  Matrix Biology [E-published May 8, doi: 10.1016/j.matbio.2015.05.003.

Abstract:  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 an RGD sequence that is not found in MAGP-1. Morpholino knockdown of MAGP-1 expression in zebrafish results 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.

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