Linked Life Data

19732768

Source:http://linkedlifedata.com/resource/pubmed/id/19732768

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
18
pubmed:dateCreated
2009-10-19
pubmed:abstractText
Lysosomes are intracellular organelles which contain enzymes and activator proteins involved in the digestion and recycling of a variety of cellular and extracellular substances. We have identified a novel sorting receptor, sortilin, which is involved in the lysosomal trafficking of the sphingolipid activator proteins, prosaposin and GM(2)AP, and the soluble hydrolases cathepsin D, cathepsin H, and acid sphingomyelinase. Sortilin belongs to a growing family of receptors with homology to the yeast Vps10 protein, which acts as a lysosomal sorting receptor for carboxypeptidase Y. In this study we examined the effects of the sortilin gene inactivation in mice. The inactivation of this gene did not yield any noticeable lysosomal pathology. To determine the existence of an alternative receptor complementing the sorting function of sortilin, we quantified the concentration of prosaposin in the lysosomes of the nonciliated epithelial cells lining the efferent ducts. These cells were chosen because they express sortilin and have a large number of lysosomes containing prosaposin. In addition, the nonciliated cells are known to endocytose luminal prosaposin that is synthesized and secreted by Sertoli cells into the seminiferous luminal fluids. Consequently, the nonciliated cells are capable of targeting both exogenous and endogenous prosaposin to the lysosomes. Using electron microscope immunogold labeling and quantitative analysis, our results demonstrate that inactivation of the sortilin gene produces a significant decrease of prosaposin in the lysosomes. When luminal prosaposin was excluded from the efferent ducts, the level of prosaposin in lysosomes was even lower in the mutant mice. Nonetheless, a significant amount of prosaposin continues to reach the lysosomal compartment. These results strongly suggest the existence of an alternative receptor that complements the function of sortilin and explains the lack of lysosomal storage disorders in the sortilin-deficient mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Vesicular..., http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin D, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsin H, http://linkedlifedata.com/resource/pubmed/chemical/Cathepsins, http://linkedlifedata.com/resource/pubmed/chemical/Ctsd protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Ctsh protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Ctsh protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Psap protein, mouse, http://linkedlifedata.com/resource/pubmed/chemical/Saposins, http://linkedlifedata.com/resource/pubmed/chemical/Sphingomyelin Phosphodiesterase, http://linkedlifedata.com/resource/pubmed/chemical/sortilin
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1090-2422
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
315
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3112-24
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The inactivation of the sortilin gene leads to a partial disruption of prosaposin trafficking to the lysosomes.
pubmed:affiliation
Department of Anatomy and Cell Biology, McGill University, Montreal, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't