The mouse <i>brown</i> (<i>b</i>) locus protein has dopachrome tautomerase activity and is located in lysosomes in transfected fibroblasts

Journal of Cell Science - Tập 106 Số 1 - Trang 153-166 - 1993
Alison J. Winder1, A Wittbjer2, Evald Rosengren2, Hans Rorsman3
1University of Oxford, South Parks Rd, Oxford OX1 3RE 1 Sir William Dunn School of Pathology , , UK
2University of Lund, S-223 62 Lund, Sweden 2 Department of Pharmacology ,
3University of Lund, S-221 85 Lund, Sweden 3 Department of Dermatology ,

Tóm tắt

ABSTRACT Many genes mapping to pigmentation loci are involved in the regulation of melanin synthesis in the mouse. The brown (b) locus controls black/brown coat coloration, and its product has significant homology to the key melanogenic enzyme tyrosinase. This has led to suggestions that the b-protein is itself a melanogenic enzyme. In order to investigate its function, we have established lines of mouse fibroblasts stably expressing the b-protein by co-transfection of a b-protein expression vector and a plasmid conferring resistance to the antibiotic G418. The b-protein synthesised by these cells has the expected molecular mass of 75 kDa and reacts with three different anti-b-protein antibodies. We were unable to confirm previous reports that the b-protein has tyrosinase or catalase activity, but detected stereospecific dopachrome tautomerase activity in b-proteinexpressing fibroblasts. This dopachrome tautomerase binds to Concanavalin A-Sepharose, and the major product of its action on L-dopachrome is 5,6-di-hydroxyindole-2-carboxylic acid. Since this activity is not present in untransfected cells we conclude that the b-protein has dopachrome tautomerase activity. Fibroblasts do not contain melanosomes, the specialised organelles in which the b-protein is located in melanocytes. Nevertheless, indirect immunofluorescence localisation of the b-protein in transfected fibroblasts produces a distinctive pattern of intense juxtanuclear staining combined with punctate cytoplasmic staining. Double-labelling shows co-localisation of the b-protein with the late endosomal/lysosomal markers β-glucuronidase and LAMP-1, both in transfected fibroblasts and in mouse melanoma cells. These findings are consistent with the hypothesis that melanosomes are closely related to lysosomes.

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Journal of Cell Science

Tập 106 Số 1

153-166

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