Deutsch
 
Hilfe Datenschutzhinweis Impressum
  DetailsucheBrowse

Datensatz

DATENSATZ AKTIONENEXPORT
Zur Ablage hinzufügen
  Lokale TagsFreigabegeschichteDetailsÜbersicht

Freigegeben
Zeitschriftenartikel

GORAB Missense Mutations Disrupt RAB6 and ARF5 Binding and Golgi Targeting

MPG-Autoren

Egerer,  Johannes
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Emmerich,  Denise
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Fischer-Zirnsak,  Björn
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Chan,  Wing Lee
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50427

Meierhofer,  David
Mass Spectrometry (Head: David Meierhofer), Scientific Service (Head: Christoph Krukenkamp), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50512

Sauer,  Sascha
Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50437

Mundlos,  Stefan
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

/persons/resource/persons50391

Kornak,  Uwe
Research Group Development & Disease (Head: Stefan Mundlos), Max Planck Institute for Molecular Genetics, Max Planck Society;

Externe Ressourcen
Es sind keine externen Ressourcen hinterlegt
Volltexte (beschränkter Zugriff)
Für Ihren IP-Bereich sind aktuell keine Volltexte freigegeben.
Volltexte (frei zugänglich)
Es sind keine frei zugänglichen Volltexte in PuRe verfügbar
Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar
Zitation

Egerer, J., Emmerich, D., Fischer-Zirnsak, B., Chan, W. L., Meierhofer, D., Tuysuz, B., et al. (2015). GORAB Missense Mutations Disrupt RAB6 and ARF5 Binding and Golgi Targeting. The Journal of Investigative Dermatology: an International Journal for Research in Cutaneous Biology, 135(10), 2368-2376. doi:10.1038/jid.2015.192.


Zitierlink: https://hdl.handle.net/11858/00-001M-0000-0028-5E99-3
Zusammenfassung
Gerodermia osteodysplastica is a hereditary segmental progeroid disorder affecting skin, connective tissues, and bone that is caused by loss-of-function mutations in GORAB. The golgin, RAB6-interacting (GORAB) protein localizes to the Golgi apparatus and interacts with the small GTPase RAB6. In this study, we used different approaches to shed more light on the recruitment of GORAB to this compartment. We show that GORAB best colocalizes with trans-Golgi markers and is rapidly displaced upon Brefeldin A exposition, indicating a loose association with Golgi membranes. A yeast two-hybrid screening revealed a specific interaction with the small GTPase ADP-ribosylation factor (ARF5) in its active, GTP-bound form. ARF5 and RAB6 bind to GORAB via the same internal Golgi-targeting RAB6 and ARF5 binding (IGRAB) domain. Two GORAB missense mutations identified in gerodermia osteodysplastica patients fall within this IGRAB domain. GORAB carrying the mutation p.Ala220Pro had a cytoplasmic distribution and failed to interact with both RAB6 and ARF5. In contrast, the p.Ser175Phe mutation displaced GORAB from the Golgi compartment to vesicular structures and selectively impaired ARF5 binding. Our findings indicate that the IGRAB domain is crucial for the Golgi localization of GORAB and that loss of this localization impairs its physiological function.