We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Molecular and computational analyses of genes involved in mannose 6-phosphate independent trafficking.
- Authors
Coutinho, M.F.; Lacerda, L.; Pinto, E.; Ribeiro, H.; Macedo‐Ribeiro, S.; Castro, L.; Prata, M.J.; Alves, S.
- Abstract
The newly-synthesized lysosomal enzymes travel to the trans-Golgi network (TGN) and are then driven to the acidic organelle. While the best-known pathway for TGN-to-endosome transport is the delivery of soluble hydrolases by the M6P receptors (MPRs), additional pathways do exist, as showed by the identification of two alternative receptors: LIMP-2, implicated in the delivery of β-glucocerebrosidase; and sortilin, involved in the transport of the sphingolipid activator proteins prosaposin and GM2AP, acid sphingomyelinase and cathepsins D and H. Disruption of the intracellular transport and delivery pathways to the lysosomes may result in lysosomal dysfunction, predictably leading to a range of clinical manifestations of lysosomal storage diseases. However, for a great percentage of patients presenting such manifestations, no condition is successfully diagnosed. To analyse if, in this group, phenotypes could be determined by impairments in the known M6P-independent receptors, we screened the genes that encode for LIMP-2 and sortilin. No pathogenic mutations were identified. Other approaches will be needed to clarify whether sortilin dysfunction may cause disease.
- Subjects
MANNOSE 6-phosphate; CATHEPSINS; LYSOSOMAL storage diseases; ENDOPLASMIC reticulum; POLYMERASE chain reaction
- Publication
Clinical Genetics, 2015, Vol 88, Issue 2, p190
- ISSN
0009-9163
- Publication type
Article
- DOI
10.1111/cge.12469