title: Caveolin-1 activates Rab5 and enhances endocytosis through direct interaction.
abstract: Caveolin-1, a constitutive protein of the caveolae, is implicated in processes of vesicular transport during caveolae-mediated endocytosis. However, the molecular mechanisms of caveolae-mediated endocytosis are not yet clearly defined. Here, we show the physiological role of the Rab5-caveolin-1 interaction during caveolae-mediated endocytosis. Rab5 was found in caveolae-enriched fractions and Rab5 directly bound to caveolin-1. Furthermore, binding sites of Rab5 to caveolin-1 were identified in the scaffold (SD), transmembrane (TM), and C-terminus (CC) domains, and the Rab5 binding domain of caveolin-1 was required for CTXB uptake. Subsequently, we performed a GST-R5BD pull-down assay to determine whether the Rab5 binding domain of caveolin-1 is involved in Rab5 activity or not. The results showed that overexpression of the Rab5 binding domain of caveolin-1 increase the amount of Rab5-GTP in Cos-1 cells. These findings imply that caveolin-1 controls the Rab5 activity during the caveolae-mediated endocytosis.
authors.affiliation: Department of Agricultural Chemistry, Graduate School of Agriculture, Tokyo University of Agriculture, 1-1-1 Sakuragaoka, Setagaya-ku, Tokyo 156-8502, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Hagiwara
authors.forename: Yukiya
authors.initials: Y
authors.lastname: Shirai
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Nomura
authors.forename: Mikio
authors.initials: M
authors.lastname: Sasaki
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Tadokoro
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D019556:COS Cells; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004705:Endocytosis; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D051381:Rats; D020696:rab5 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C495537:Cav1 protein, rat; D051242:Caveolin 1; D020696:rab5 GTP-Binding Proteins