Molecular and computational analyses of genes involved in mannose 6‐phosphate independent trafficking. (17th September 2014)

• Record Type: Journal Article
• Authors: Coutinho, M.F.; Lacerda, L.; Pinto, E.; Ribeiro, H.; Macedo‐Ribeiro, S.; Castro, L.; Prata, M.J.; Alves, S.
• Is Part Of: Clinical genetics. Volume 88:Number 2(2015:Aug.)
• Page Start: 190
• Page End: 194
• Publication Date: 2014-09-17
• Subjects: Medical genetics -- Periodicals; 616.0420
• DOI: 10.1111/cge.12469
• Languages: English
• ISSNs: 0009-9163

Abstract

<abstract abstract-type="main" id="cge12469-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p id="cge12469-para-0001">The newly‐synthesized lysosomal enzymes travel to the <italic>trans</italic>‐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.</p> </abstract>