SLC30A10 is a cell surface-localized manganese efflux transporter

dc.contributor.author	Leyva-Illades, Dinorah	en
dc.contributor.author	Chen, Pan	en
dc.contributor.author	Ζόγκζας, Νικόλαος Π.	el
dc.contributor.author	Hutchens, Steven	en
dc.contributor.author	Mercado, Jonathan M.	en
dc.date.accessioned	2015-05-27T07:12:23Z
dc.date.available	2015-05-27T07:12:23Z
dc.date.issued	2015-05-27
dc.identifier.uri	http://hdl.handle.net/11400/11220
dc.rights	Αναφορά Δημιουργού-Μη Εμπορική Χρήση-Όχι Παράγωγα Έργα 3.0 Ηνωμένες Πολιτείες	*
dc.rights.uri	http://creativecommons.org/licenses/by-nc-nd/3.0/us/	*
dc.source	http://www.jneurosci.org/content/34/42/14079	el
dc.subject	Manganese
dc.subject	Efflux
dc.subject	Εκροή
dc.subject	GPP130
dc.subject	Μαγγάνιο
dc.subject	Parkinsonism
dc.subject	Παρκινσονισμός
dc.subject	SLC30A10
dc.subject	Trafficking
dc.subject	Εμπορία
dc.title	SLC30A10 is a cell surface-localized manganese efflux transporter	en
heal.type	journalArticle
heal.secondaryTitle	and parkinsonism-causing mutations block its intracellular trafficking and efflux activity	en
heal.classification	Chemical technology
heal.classification	Food technology
heal.classification	Χημική τεχνολογία
heal.classification	Τεχνολογία τροφίμων
heal.classificationURI	http://skos.um.es/unescothes/C00565
heal.classificationURI	http://skos.um.es/unescothes/C01577
heal.classificationURI	N/A-Χημική τεχνολογία
heal.classificationURI	N/A-Τεχνολογία τροφίμων
heal.keywordURI	http://zbw.eu/stw/descriptor/14301-2
heal.contributorName	Swaim, Caleb D.	en
heal.contributorName	Morrisett, Richard A.	en
heal.contributorName	Bowman, Aaron B.	en
heal.contributorName	Aschner, Michael	el
heal.contributorName	Mukhopadhyay, Somshuvra	en
heal.identifier.secondary	DOI: 10.1523/JNEUROSCI.2329-14.2014
heal.identifier.secondary	ISSN: 02706474
heal.language	en
heal.access	campus
heal.recordProvider	Τεχνολογικό Εκπαιδευτικό Ίδρυμα Αθήνας. Σχολή Τεχνολογίας Τροφίμων & Διατροφής. Τμήμα Τεχνολογίας Τροφίμων	el
heal.publicationDate	2014-10-15
heal.bibliographicCitation	Leyva-Illades, D., Chen, P., Zogzas, N. P., Hutchens, S., Mercado, J. M., et.al. (2014). SLC30A10 is a cell surface-localized manganese efflux transporter: and parkinsonism-causing mutations block its intracellular trafficking and efflux activity. "Journal of Neuroscience", 34(42), 15 October 2014. pp 14079-14095. Available from: http://www.jneurosci.org/content/34/42/14079. [Accessed 10/09/2014]	en
heal.abstract	Manganese (Mn) is an essential metal, but elevated cellular levels are toxic and may lead to the development of an irreversible parkinsonian-like syndrome that has no treatment. Mn-induced parkinsonism generally occurs as a result of exposure to elevated Mn levels in occupational or environmental settings. Additionally, patients with compromised liver function attributable to diseases, such as cirrhosis, fail to excrete Mn and may develop Mn-induced parkinsonism in the absence of exposure to elevated Mn. Recently, a new form of familial parkinsonism was reported to occur as a result of mutations in SLC30A10. The cellular function of SLC30A10 and the mechanisms by which mutations in this protein cause parkinsonism are unclear. Here, using a combination of mechanistic and functional studies in cell culture, Caenorhabditis elegans, and primary midbrain neurons, we show that SLC30A10 is a cell surface-localized Mn efflux transporter that reduces cellular Mn levels and protects against Mn-induced toxicity. Importantly, mutations in SLC30A10 that cause familial parkinsonism blocked the ability of the transporter to traffic to the cell surface and to mediate Mn efflux. Although expression of disease-causing SLC30A10 mutations were not deleterious by themselves, neurons and worms expressing these mutants exhibited enhanced sensitivity to Mn toxicity. Our results provide novel insights into the mechanisms involved in the onset of a familial form of parkinsonism and highlight the possibility of using enhanced Mn efflux as a therapeutic strategy for the potential management of Mn-induced parkinsonism, including that occurring as a result of mutations in SLC30A10.	en
heal.publisher	Society for Neuroscience	en
heal.journalName	Journal of Neuroscience	en
heal.journalType	peer-reviewed
heal.fullTextAvailability	true