title: A neural-specific F-box protein Fbs1 functions as a chaperone suppressing glycoprotein aggregation.
abstract: Fbs1 is an F-box protein present abundantly in the nervous system. Similar to the ubiquitously expressed Fbs2, Fbs1 recognizes N-glycans at the innermost position as a signal for unfolded glycoproteins, probably in the endoplasmic reticulum-associated degradation pathway. Here, we show that the in vivo majority of Fbs1 is present as Fbs1-Skp1 heterodimers or Fbs1 monomers but not SCF(Fbs1) complex. The inefficient SCF complex formation of Fbs1 and the restricted presence of SCF(Fbs1) bound on the endoplasmic reticulum membrane were due to the short linker sequence between the F-box domain and the sugar-binding domain. In vitro, Fbs1 prevented the aggregation of the glycoprotein through the N-terminal unique sequence of Fbs1. Our results suggest that Fbs1 assists clearance of aberrant glycoproteins in neuronal cells by suppressing aggregates formation, independent of ubiquitin ligase activity, and thus functions as a unique chaperone for those proteins.
authors.affiliation: Tokyo Metropolitan Institute of Medical Science, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8613. yyosida@rinshoken.or.jp
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Arisa
authors.initials: A
authors.lastname: Murakami
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Iwai
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D019281:Dimerization; D044783:F-Box Proteins / Q000032:analysis* / Q000737:chemistry / Q000502:physiology*; D006023:Glycoproteins / Q000737:chemistry; D051379:Mice; D018832:Molecular Chaperones / Q000502:physiology*; D016716:PC12 Cells; D011489:Protein Denaturation; D051381:Rats; D044843:SKP Cullin F-Box Protein Ligases / Q000502:physiology*
chemical_list: D044783:F-Box Proteins; D006023:Glycoproteins; D018832:Molecular Chaperones; D044843:SKP Cullin F-Box Protein Ligases