Rer1p maintains ciliary length and signaling by regulating γ-secretase activity and Foxj1a levels
| Autor: | Veerle Baert, H. Joseph Yost, Nathalie Jurisch-Yaksi, Przemko Tylzanowski, Tim Raemaekers, Applonia Josephine Rose, Guy Froyen, Wendy Vermeire, Cammon B. Arrington, Huiqi Lu, Roel Vandepoel, Emre Yaksi, Daphne Verleyen, Wim Annaert, Pieter Baatsen, Sebastian Munck, Thomy de Ravel, Suzie J. Scales |
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| Přispěvatelé: | Frailty in Ageing, Gerontology, Clinical sciences, Medical Genetics |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Swine
Notch signaling pathway Biology Ciliopathies Cell Line 03 medical and health sciences 0302 clinical medicine Cilia/genetics Ciliogenesis Report Animals Humans Cilia Zebrafish Research Articles 030304 developmental biology 0303 health sciences Amyloid Precursor Protein Secretases/genetics Receptors Notch/genetics Membrane Glycoproteins Receptors Notch Gene Expression Regulation/physiology Signal Transduction/physiology Cilium Endoplasmic reticulum Forkhead Transcription Factors/biosynthesis Forkhead Transcription Factors Cell Biology Membrane Glycoproteins/genetics Zebrafish Proteins biology.organism_classification Hedgehog signaling pathway Cell biology Adaptor Proteins Vesicular Transport Gene Expression Regulation Signal transduction Amyloid Precursor Protein Secretases 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 0021-9525 |
| Popis: | Rer1p is an ER/cis-Golgi membrane protein that maintains ciliary length and function by reducing γ-secretase complex assembly and activity (thereby balancing Notch signaling) and increasing Foxj1a expression. 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. |
| Databáze: | OpenAIRE |
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