Hyaluronan synthase

Hyaluronan synthases (HAS) are membrane-bound enzymes which use UDP-α-N-acetyl-D-glucosamine and UDP-α-D-glucuronate as substrates to produce the glycosaminoglycan hyaluronan at the cell surface and extrude it through the membrane into the extracellular space.

Isoforms

There are three mammalian hyaluronan synthases described to date - HAS1, HAS2 and HAS3. Each of these isoforms resides at a different chromosome location [Spicer AP et al. (1997) Chromosomal localization of the human and mouse hyaluronan synthase genes. Genomics 41:493-497.] and has been cloned. [Itano N and Kimata K (2002) Mammalian hyaluronan synthases. IUBMB Life 54:195-199.] Two of the main differences between the isoforms are the chain length of the hyaluronan molecules that they produce and the ease with which they can be released from the cell surface. [Itano N et al. (1999) Three isoforms of mammalian hyaluronan synthases have distinct enzymatic properties. J Biol Chem 274:25085-25092.] [Stern R, et al. (2006) Hyaluronan fragments: an information-rich system. Eur J Cell Biol 85:699-715.] When mammalian cells are stimulated by changes in their immediate environment (cytokines, extracellular matrix proximities), the HAS isoforms respond differently and appear to be under different control mechanisms.

During the development of the embryo, each isoform is uniquely expressed, both spatially and temporally.
* HAS2 is probably the most important synthase at this time as mice lacking the ability to express HAS2 (knock-out mice) die at mid-gestation, [Camenisch TD et al. (2000) Disruption of hyaluronan synthase-2 abrogates normal cardiac morphogenesis and hyaluronan-mediated transformation of epithelium to mesenchyme. J Clin Invest 106:349-360.]
* HAS1 or HAS3 knock-out mice show no effect on foetal developmentFact|date=September 2007.

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