title: Rer1p maintains ciliary length and signaling by regulating γ-secretase activity and Foxj1a levels.
abstract: Cilia project from the surface of most vertebrate cells and are important for several physiological and developmental processes. Ciliary defects are linked to a variety of human diseases, named ciliopathies, underscoring the importance of understanding signaling pathways involved in cilia formation and maintenance. In this paper, we identified Rer1p as the first endoplasmic reticulum/cis-Golgi-localized membrane protein involved in ciliogenesis. Rer1p, a protein quality control receptor, was highly expressed in zebrafish ciliated organs and regulated ciliary structure and function. Both in zebrafish and mammalian cells, loss of Rer1p resulted in the shortening of cilium and impairment of its motile or sensory function, which was reflected by hearing, vision, and left-right asymmetry defects as well as decreased Hedgehog signaling. We further demonstrate that Rer1p depletion reduced ciliary length and function by increasing γ-secretase complex assembly and activity and, consequently, enhancing Notch signaling as well as reducing Foxj1a expression.
authors.affiliation: VIB Center for the Biology of Disease, KULeuven, 3000 Leuven, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Jurisch-Yaksi
authors.forename: Applonia J
authors.initials: AJ
authors.lastname: Rose
authors.forename: Huiqi
authors.initials: H
authors.lastname: Lu
authors.forename: Tim
authors.initials: T
authors.lastname: Raemaekers
authors.forename: Sebastian
authors.initials: S
authors.lastname: Munck
authors.forename: Pieter
authors.initials: P
authors.lastname: Baatsen
authors.forename: Veerle
authors.initials: V
authors.lastname: Baert
authors.forename: Wendy
authors.initials: W
authors.lastname: Vermeire
authors.forename: Suzie J
authors.initials: SJ
authors.lastname: Scales
authors.forename: Daphne
authors.initials: D
authors.lastname: Verleyen
authors.forename: Roel
authors.initials: R
authors.lastname: Vandepoel
authors.forename: Przemko
authors.initials: P
authors.lastname: Tylzanowski
authors.forename: Emre
authors.initials: E
authors.lastname: Yaksi
authors.forename: Thomy
authors.initials: T
authors.lastname: de Ravel
authors.forename: H Joseph
authors.initials: HJ
authors.lastname: Yost
authors.forename: Guy
authors.initials: G
authors.lastname: Froyen
authors.forename: Cammon B
authors.initials: CB
authors.lastname: Arrington
authors.forename: Wim
authors.initials: W
authors.lastname: Annaert
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002923:Cilia / Q000235:genetics / Q000378:metabolism; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D013552:Swine; D015027:Zebrafish; D029961:Zebrafish Proteins
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; C533681:Foxj1a protein, zebrafish; D008562:Membrane Glycoproteins; C109546:RER1 protein, human; D051880:Receptors, Notch; D029961:Zebrafish Proteins; D053829:Amyloid Precursor Protein Secretases