INTER-ALPHA-TRYPSIN INHIBITOR PROTEOGLYCAN FAMILY - A GROUP OF PROTEINS BINDING AND STABILIZING THE EXTRACELLULAR-MATRIX

Extracellular matrix (ECM) is composed of several macromolecules assoc iated in a complex network. This structure allows cells to adhere, mig rate and interact. Hyaluronic acid (HA) is a glycosaminoglycan (GAG) a nd a major representative of ECM. HA-binding proteins such as CD44, ag grecan, and versican, have been implicated in structuring the ECM by s tabilizing large macromolecular aggregates. They also play an importan t role in tumor metastasis and cell motility. Recently, further HA-bin ding proteins were identified: the inter-alpha-trypsin inhibitor(ITI)- related proteins. ITI is a glycoprotein composed of three polypeptides : two heavy chains (HC1 and HC2) and one light chain (bikunin). Bikuni n confers the prelease-inhibitor function. The heavy chains' function was unknown. Recent studies have shown that HC1 and HC2 are linked in vivo and in vitro to hyaluronic acid. This linkage greatly improves ex tracellular matrix stability. It also demonstrates that ITI-related pr oteins might be considered as HA-binding proteins (HABP). The ITI rela ted proteins are composed of four polypeptides (HC1, HC2, HC3 and the bikunin) encoded by four genes H1, H2, H3 and L. Unlike the majority o f plasma protein a non-disulfide covalent linkage exists between heavy chains and bikunin. This review presents the recent progress concerni ng the interactions between ITI and ECM showing that ITI-related prote ins are HABP members. We will focus on the heavy chain linkage with HA , which represents the demonstration of covalent binding between prote ins and HA.