Malaria-suppressible expression of the anti-apoptotic triple GTPase mGIMAP8.

The IMAP/IAN family of AIG1-like GTPases is conserved among vertebrates and angiosperm plants and has been postulated to regulate apoptosis, particularly in context with diseases such as cancer, diabetes, and infections. The human genes were recently renamed as gimap for GTPase of the immunity associated protein (GIMAP) family. Here we extend this new nomenclature to the murine gimap gene family. All gimap genes of the mouse are clustered on chromosome 6B with eight functional members and one pseudogene. The mGIMAP proteins contain one GTP-binding site and display molecular masses between 33 and 38 kDa except for the very unusual 77 kDa mGIMAP8 protein, which is the first characterized protein containing three GTP-binding domains. Northern blot analysis revealed expression of mgimap8 predominantly in the thymus. The low expression level observed in the spleen was further suppressed by Plasmodium chabaudi malaria. Confocal laser scanning microscopy demonstrated localization of mGIMAP8 at ER, Golgi, and mitochondria. Overexpression of mGIMAP8 could significantly impair anisomycin-induced activation of caspase 3. Our data support the view that mGIMAP8 exerts an anti-apoptotic effect in the immune system and is involved in responses to infections.

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