The ubiquitously expressed MURR1 protein is absent in canine copper toxicosis
2003; Elsevier BV; Volume: 39; Issue: 5 Linguagem: Inglês
10.1016/s0168-8278(03)00380-5
ISSN1600-0641
AutoresAdriana E.M. KLOMP, Bart van de Sluis, Leo W. J. Klomp, Cisca Wijmenga,
Tópico(s)Drug Transport and Resistance Mechanisms
ResumoAbstract Background/Aims : Copper toxicosis (CT) in Bedlington terriers is an autosomal recessive disorder characterized by massive lysosomal copper accumulation in livers of affected dogs, and a defect in the biliary excretion of this metal. We propose that MURR1 , the gene defective in canine CT, has a role in the regulation of copper excretion into bile during copper overload. Methods : Polyclonal antibodies raised against full-length recombinant human MURR1 were used for immunoblot analysis and indirect immunofluorescence studies. Results : Using Western blot analysis, these antibodies abundantly detected MURR1 as a 23 kDa protein in liver extracts of mice and dogs, but MURR1 was undetectable in the livers of affected Bedlington terriers. MURR1 was also detected in different tissues and cell lines; in cell lines the protein was found both in cytosol and membrane preparations. Consistent with this observation, indirect immunofluorescence staining revealed that in some cells MURR1 was associated with a vesicular compartment diffusely localized throughout the cell. Conclusions : The genomic deletion in MURR1 results in complete absence of MURR1 protein. Based on the unanticipated subcellular localization, our results suggest a role for MURR1 in the regulation of vesicular copper sequestration during copper overload.
Referência(s)