title: Rab10-mediated endocytosis of the hyaluronan synthase HAS3 regulates hyaluronan synthesis and cell adhesion to collagen.
abstract: Hyaluronan synthases (HAS1-3) are unique in that they are active only when located in the plasma membrane, where they extrude the growing hyaluronan (HA) directly into cell surface and extracellular space. Therefore, traffic of HAS to/from the plasma membrane is crucial for the synthesis of HA. In this study, we have identified Rab10 GTPase as the first protein known to be involved in the control of this traffic. Rab10 colocalized with HAS3 in intracellular vesicular structures and was co-immunoprecipitated with HAS3 from isolated endosomal vesicles. Rab10 silencing increased the plasma membrane residence of HAS3, resulting in a significant increase of HA secretion and an enlarged cell surface HA coat, whereas Rab10 overexpression suppressed HA synthesis. Rab10 silencing blocked the retrograde traffic of HAS3 from the plasma membrane to early endosomes. The cell surface HA coat impaired cell adhesion to type I collagen, as indicated by recovery of adhesion following hyaluronidase treatment. The data indicate a novel function for Rab10 in reducing cell surface HAS3, suppressing HA synthesis, and facilitating cell adhesion to type I collagen. These are processes important in tissue injury, inflammation, and malignant growth.
authors: From the Institutes of Biomedicine.
authors: Ashik Jawahar
authors: AJ
authors: Deen
authors: Kirsi
authors: K
authors: Rilla
authors: Sanna
authors: S
authors: Oikari
authors: Riikka
authors: R
authors: Kärnä
authors: Genevieve
authors: G
authors: Bart
authors: Jukka
authors: J
authors: Häyrinen
authors: Avinash Rahul
authors: AR
authors: Bathina
authors: Antti
authors: A
authors: Ropponen
authors: Katri
authors: K
authors: Makkonen
authors: Raija H
authors: RH
authors: Tammi
authors: Markku I
authors: MI
authors: Tammi
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D024042:Collagen Type I / Q000378:metabolism*; D004285:Dogs; D004705:Endocytosis; D014453:Glucuronosyltransferase / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D021381:Protein Transport; D034622:RNA Interference; D015854:Up-Regulation; D020691:rab GTP-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C105458:HAS3 protein, human; D000076002:Hyaluronan Synthases; C538901:Rab10 protein, human; D020691:rab GTP-Binding Proteins
keywords: Cell Adhesion; Collagen; Endocytosis; Hyaluronate; Intracellular Trafficking; Rab Proteins; Vesicles