Molecular control of the hyaluronan biosynthesis.
Hyaluronan (HA) is the only unsulfated glycosaminoglycan (GAG) composed of repeating units of D-glucuronic acid and N-acetylglucosamine. The amount and the molecular weight of HA are important factors that regulate the physiology and pathology in several mammalian tissues. In fact hydrated HA makes ECM an ideal environment in which cells can move and proliferate. HA interacting with several receptors at the cellular level plays a critical role in signal transduction responses. The control of the HA synthesis is therefore a critical aspect in ECM and cells biology, but so far the information about this question is scanty. The synthesis of HA is due to several enzymes activities which not only involves its synthetic enzymes on the membranes of the cells (HA synthases 1, 2, 3, isoforms) but also the cytoplasmatic enzymes producing the UDP-sugar precursors. The UDP-sugars availability in cytoplasm is a critical point for the GAG synthesis and it seems to affect particularly the HA production. Eventually, the activity control of the enzymes involved in HA metabolism is obtained throughout both enzyme amount and their postsynthetic covalent modification, as phosphorylation. In fact, it was recently reported that HA synthase 3 may be phosphorylated after specific stimuli, and an increasing body of evidence supports the idea that the synthetic pathway of HA may be carefully regulated in all steps.
Viola
Manuela
M
Dipartimento di Scienze Biomediche Sperimentali e Cliniche, Universita' Degli Studi dell'Insubria, Varese, Italy.
Vigetti
Davide
D
Genasetti
Anna
A
Rizzi
Manuela
M
Karousou
Evgenia
E
Moretto
Paola
P
Clerici
Moira
M
Bartolini
Barbara
B
Pallotti
Francesco
F
De Luca
Giancarlo
G
Passi
Alberto
A
D000818:Animals; D005109:Extracellular Matrix / Q000378:metabolism*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000096:biosynthesis* / Q000502:physiology; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D014532:Uridine Diphosphate Glucose / Q000378:metabolism; D014533:Uridine Diphosphate Glucose Dehydrogenase / Q000378:metabolism
D006820:Hyaluronic Acid; D014533:Uridine Diphosphate Glucose Dehydrogenase; D014453:Glucuronosyltransferase; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase; D014532:Uridine Diphosphate Glucose