Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome.

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 pro...

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Autores principales:	Claudia Orelio, Renée M van der Sluis, Paul Verkuijlen, Micha Nethe, Peter L Hordijk, Timo K van den Berg, Taco W Kuijpers
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1883982f42954caaa8f20dbb64ebef6b
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spelling	oai:doaj.org-article:1883982f42954caaa8f20dbb64ebef6b2021-11-18T06:52:12ZAltered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome.1932-620310.1371/journal.pone.0020727https://doaj.org/article/1883982f42954caaa8f20dbb64ebef6b2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21695142/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Shwachman-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.Claudia OrelioRenée M van der SluisPaul VerkuijlenMicha NethePeter L HordijkTimo K van den BergTaco W KuijpersPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 6, p e20727 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Claudia Orelio Renée M van der Sluis Paul Verkuijlen Micha Nethe Peter L Hordijk Timo K van den Berg Taco W Kuijpers Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome.
description	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.
format	article
author	Claudia Orelio Renée M van der Sluis Paul Verkuijlen Micha Nethe Peter L Hordijk Timo K van den Berg Taco W Kuijpers
author_facet	Claudia Orelio Renée M van der Sluis Paul Verkuijlen Micha Nethe Peter L Hordijk Timo K van den Berg Taco W Kuijpers
author_sort	Claudia Orelio
title	Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome.
title_short	Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome.
title_full	Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome.
title_fullStr	Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome.
title_full_unstemmed	Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome.
title_sort	altered intracellular localization and mobility of sbds protein upon mutation in shwachman-diamond syndrome.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/1883982f42954caaa8f20dbb64ebef6b
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Altered intracellular localization and mobility of SBDS protein upon mutation in Shwachman-Diamond syndrome.

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