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bioRxiv · 10.1101/245423

The abnormal, mis-localizated HR bmh protein associates with members of the protein processing machinery in the cytoplasm

Folco, E. G.·Brancaz-Bouvier, M.-V.·Belly, A.·Nonchev, S.
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Abstract

We have recently mapped a 296 bp deletion at the mouse hairless locus that causes the mutation hairless rhino bald Mill Hill, (Hrrhbmh), (ID:MGI:3039558; J:89321), removing the stop codon and generating a larger mutant protein HR bmh with an additional sequence of 117 amino acids. The mutant hairless gene mRNA is expressed during the embryonic and post-natal development of the hair follicle. A mutant HR protein was identified in bmh mouse skin at different stages of development by a specific antibody. We demonstrated that the HR bmh protein is able to interact with the vitamin D receptor, but is not able to repress VDR-mediated transactivation. Immunofluorescence analysis revealed that HR bmh protein displays an abnormal cellular localization in transfected cell lines, as well as in the epidermis and hair follicle of bmh mutant mice. Here we analyse the patterns of HR bmh extra-nuclear localization in cell transfection experiments. Using a candidate approach, double transfection experiments, immunofluorescent staining and IP protocols we established that HR bmh co-localizes specifically with the proteins HDAC6 in the cytoplasm is able to physically interact with it. Blast analysis allowed to show that HDAC6 and share high sequence homologies with specific motifs of HR bmh. We studied the association of these potential interactors with various cytoplasmic compartments. We discuss the relevance of the mutant hairless protein mis-localization in endosomal processing and in proteasome related pathways with respect to the specific skin phenotype of mouse hairless mutants.

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Folco, E. G., Brancaz-Bouvier, M.-V., Belly, A., Nonchev, S.. 2018-01-09. The abnormal, mis-localizated HR bmh protein associates with members of the protein processing machinery in the cytoplasm. https://doi.org/10.1101/245423

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