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dc.contributor.author
Yuan, Libin
dc.contributor.author
Carvelli, Flavia Lorena
dc.contributor.author
Morales, Carlos R.
dc.contributor.other
Méndez Vilas, Antonio
dc.date.available
2020-06-10T18:43:44Z
dc.date.issued
2012
dc.identifier.citation
Yuan, Libin; Carvelli, Flavia Lorena; Morales, Carlos R.; Dynamic microscopy: Reconstructing a novel lysosomal trafficking pathway; Formatex Research Center; 1; 2012; 445-457
dc.identifier.isbn
978-84-939843-5-9
dc.identifier.uri
http://hdl.handle.net/11336/107217
dc.description.abstract
The delivery of newly synthesized lysosomal proteins to endosomes and lysosomes is dependent on several functionally distinct compartments, i.e., the endoplasmic reticulum (ER), the Golgi apparatus and small carrier vesicles. These compartments also play a role in the synthesis, post-translational modification, sorting and distribution of proteins to other destinations. In fact, most cargo is sorted within, and exits from, the trans-Golgi network (TGN). Proteins delivered to the endosomal/lysosomal system include a large and diverse class of hydrolytic enzymes and non-enzymatic activator proteins that were thought to be directed to the lysosomes by their binding to mannose-6-phosphate receptors (MPRs). Surprisingly, in I-cell disease, in which the MPR pathway is disrupted, the non-enzymatic sphingolipid activator protein, prosaposin, continues to traffic to lysosomes. The use of dynamic immunoconfocal and immunoelectron microscopy along with mutational analysis and chimeric protein technology led us to the discovery of a new lysosomal sorting receptor, sortilin. We found that prosaposin is targeted to the lysosomes through an interaction with sortilin. Deletion of the C-terminus of prosaposin abolished its transport to the lysosomes, and mutational analysis revealed that the first half of the prosaposin C-terminus (aa524-540) contains a motif required for its binding to sortilin and its transport to lysosomes. Additionally, a chimeric construct consisting of albumin and a distal segment of prosaposin, which includes its C-terminus, resulted in the routing of albumin to lysosomes. In conclusion, we have identified a specific region in the C-terminus of prosaposin, as well as amino acid residues that are critical for the binding of prosaposin to sortilin and its subsequent lysosomal trafficking.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Formatex Research Center
dc.rights
info:eu-repo/semantics/restrictedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
MICROSCOPY
dc.subject
LYSOSOME
dc.subject
TRAFFIC-PATHWAY
dc.subject.classification
Bioquímica y Biología Molecular
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Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
Dynamic microscopy: Reconstructing a novel lysosomal trafficking pathway
dc.type
info:eu-repo/semantics/publishedVersion
dc.type
info:eu-repo/semantics/bookPart
dc.type
info:ar-repo/semantics/parte de libro
dc.date.updated
2020-05-11T15:40:36Z
dc.journal.volume
1
dc.journal.pagination
445-457
dc.journal.pais
España
dc.journal.ciudad
Badajoz
dc.description.fil
Fil: Yuan, Libin. McGill University; Canadá
dc.description.fil
Fil: Carvelli, Flavia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Histología y Embriología D/mend Dr.m.burgos; Argentina
dc.description.fil
Fil: Morales, Carlos R.. McGill University; Canadá
dc.conicet.paginas
788
dc.source.titulo
Current Microscopy Contributions to Advances in Science and Technology
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