title: The high and low molecular weight forms of hyaluronan have distinct effects on CD44 clustering.
abstract: CD44 is a major cell surface receptor for the glycosaminoglycan hyaluronan (HA). Native high molecular weight hyaluronan (nHA) and oligosaccharides of hyaluronan (oHA) provoke distinct biological effects upon binding to CD44. Despite the importance of such interactions, however, the feature of binding with CD44 at the cell surface and the molecular basis for functional distinction between different sizes of HA is still unclear. In this study we investigated the effects of high and low molecular weight hyaluronan on CD44 clustering. For the first time, we provided direct evidence for a strong relationship between HA size and CD44 clustering in vivo. In CD44-transfected COS-7 cells, we showed that exogenous nHA stimulated CD44 clustering, which was disrupted by oHA. Moreover, naturally expressed CD44 was distributed into clusters due to abundantly expressed nHA in HK-2 cells (human renal proximal tubule cells) and BT549 cells (human breast cancer cell line) without exogenous stimulation. Our results suggest that native HA binding to CD44 selectively induces CD44 clustering, which could be inhibited by oHA. Finally, we demonstrated that HA regulates cell adhesion in a manner specifically dependent on its size. oHA promoted cell adhesion while nHA showed no effects. Our results might elucidate a molecular- and/or cellular-based mechanism for the diverse biological activities of nHA and oHA.
authors.affiliation: Department of Molecular Biology Laboratory, Shanghai Jiaotong University School of Medicine, Shanghai 200233, China.
authors.forename: Cuixia
authors.initials: C
authors.lastname: Yang
authors.forename: Manlin
authors.initials: M
authors.lastname: Cao
authors.forename: Hua
authors.initials: H
authors.lastname: Liu
authors.forename: Yiqing
authors.initials: Y
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Yan
authors.initials: Y
authors.lastname: Du
authors.forename: Yiwen
authors.initials: Y
authors.lastname: Liu
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Wang
authors.forename: Lian
authors.initials: L
authors.lastname: Cui
authors.forename: Jiajie
authors.initials: J
authors.lastname: Hu
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
mesh_terms: D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion / Q000187:drug effects; D002522:Chlorocebus aethiops; D016000:Cluster Analysis; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism*; D006820:Hyaluronic Acid / Q000737:chemistry* / Q000378:metabolism*; D007150:Immunohistochemistry; D008970:Molecular Weight; D009844:Oligosaccharides / Q000378:metabolism; D038761:Photobleaching / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014162:Transfection
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors; D009844:Oligosaccharides; D047428:Protein Kinase Inhibitors; D011993:Recombinant Fusion Proteins; D006820:Hyaluronic Acid