Enzymatic Activity of the Cell Surface Hyaluronan-Degrading Enzyme TMEM2 and the Phenotype of Its Knockout Mice

Abstract

Hyaluronan, a large linear glycopolymer, is a major component of the extracellular matrix (ECM) and is abundant in both the blood and lymph fluids. Its diverse biological functions have been investigated with deficient mouse in enzymes responsible for synthesis, binding, and degradation. Recently, the enzymes responsible for the extracellular degradation of hyaluronan, specifically cell migration-inducing protein (CEMIP)/HYBID and transmembrane protein-2 (TMEM2)/CEMIP2, have been identified. These enzymes were previously considered to have missing links in the hyaluronan metabolism and their discovery has garnered significant attention owing to their biological importance. This article focuses on the hyaluronidases responsible for hyaluronan degradation, emphasizing the differences between TMEM2/CEMIP2, a transmembrane hyaluronan-degrading enzyme, and other previously characterized hyaluronidases. Additionally, this article presents the cellular responses associated with the extracellular hyaluronan degradation activity, as reported in the literature.