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Renée Marije van der Sluis

Altered Intracellular Localization and Mobility of SBDS Protein upon Mutation in Shwachman-Diamond Syndrome

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

  • Claudia Orelio, Sanquin Research and Landsteiner Laboratory of the Academic Medical Center (AMC), Department of Blood Cell Research, University of Amsterdam, Amsterdam, The Netherlands, Holland
  • Renée Marije van der Sluis
  • Paul Verkuilen, Sanquin Research and Landsteiner Laboratory of the Academic Medical Center (AMC), Department of Blood Cell Research, University of Amsterdam, Amsterdam, The Netherlands, Holland
  • Micha Nethe, Sanquin Research and Landsteiner Laboratory of the Academic Medical Center (AMC), Department of Molecular Cell Biology, University of Amsterdam, Amsterdam, The Netherlands, Holland
  • Peter L Hordijk, Sanquin Research and Landsteiner Laboratory of the Academic Medical Center (AMC), Department of Molecular Cell Biology, University of Amsterdam, Amsterdam, The Netherlands, Holland
  • Timo K van den Berg, Sanquin Research and Landsteiner Laboratory of the Academic Medical Center (AMC), Department of Blood Cell Research, University of Amsterdam, Amsterdam, The Netherlands, Holland
  • Taco W Kuijpers, Sanquin Research and Landsteiner Laboratory of the Academic Medical Center (AMC), Department of Blood Cell Research, University of Amsterdam, Amsterdam, The Netherlands, Emma Children's Hospital, Academic Medical Center (AMC), Amsterdam, The Netherlands, Mayo Clinic, United States of America, Holland
Shwachman-Diamond Syndrome (SDS) is a rare inherited disease caused by mutations in the SBDS gene. Hematopoietic defects, exocrine pancreas dysfunction and short stature are the most prominent clinical features. To gain understanding of the molecular properties of the ubiquitously expressed SBDS protein, we examined its intracellular localization and mobility by live cell imaging techniques. We observed that SBDS full-length protein was localized in both the nucleus and cytoplasm, whereas patient-related truncated SBDS protein isoforms localize predominantly to the nucleus. Also the nucleo-cytoplasmic trafficking of these patient-related SBDS proteins was disturbed. Further studies with a series of SBDS mutant proteins revealed that three distinct motifs determine the intracellular mobility of SBDS protein. A sumoylation motif in the C-terminal domain, that is lacking in patient SBDS proteins, was found to play a pivotal role in intracellular motility. Our structure-function analyses provide new insight into localization and motility of the SBDS protein, and show that patient-related mutant proteins are altered in their molecular properties, which may contribute to the clinical features observed in SDS patients.
OriginalsprogEngelsk
TidsskriftP L o S One
Sider (fra-til)e20727
ISSN1932-6203
DOI
StatusUdgivet - 2011
Eksternt udgivetJa

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