Autor(es): Coutinho, M.F. ; Lacerda, L. ; Pinto, E. ; Ribeiro, H. ; Macedo-Ribeiro, S. ; Castro, L. ; Prata, M.J. ; Alves, S.
Data: 2014
Identificador Persistente: http://hdl.handle.net/10400.18/2850
Origem: Repositório Científico do Instituto Nacional de Saúde
Assunto(s): Doenças Genéticas; Genética Humana; Doenças Lisossomais de Sobrecarga; LIMP-2; M6P Independent Trafficking; Lysosomal Storage Diseases; Sortilin
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.
