Abstract
BackgroundRab GTPases are regulators of intracellular membrane traffic. The Rab27 subfamily consists of Rab27a and Rab27b. Rab27a has been recently implicated in Griscelli Disease, a disease combining partial albinism with severe immunodeficiency. Rab27a plays a key role in the function of lysosomal-like organelles such as melanosomes in melanocytes and lytic granules in cytotoxic T lymphocytes. Little is known about Rab27b.ResultsThe human RAB27B gene is organised in six exons, spanning about 69 kb in the chromosome 18q21.1 region. Exon 1 is non-coding and is separated from the others by 49 kb of DNA and exon 6 contains a long 3' untranslated sequence (6.4 kb). The mouse Rab27b cDNA shows 95% identity with the human cDNA at the protein level and maps to mouse chromosome 18. The mouse mRNA was detected in stomach, large intestine, spleen and eye by RT-PCR, and in heart, brain, spleen and kidney by Northern blot. Transient over-expression of EGF-Rab27b fusion protein in cultured melanocytes revealed that Rab27b is associated with melanosomes, as observed for EGF-Rab27a.ConclusionsOur results indicate that the Rab27 subfamily of Ras-like GTPases is highly conserved in mammals. There is high degree of conservation in sequence and gene structure between RAB27A and RAB27B genes. Exogenous expression of Rab27b in melanocytes results in melanosomal association as observed for Rab27a, suggesting the two Rab27 proteins are functional homologues. As with RAB27A in Griscelli Disease, RAB27B may be also associated with human disease mapping to chromosome 18.
Highlights
Rab GTPases are regulators of intracellular membrane traffic
Rab27a was initially cloned from a megakaryocyte library and subsequent studies revealed that it is expressed in haemopoietic-derived cells, melanocytes in skin and eye, lung, pancreas and intestine [5,7,8]
Hybridization of the RAB27B cDNA (U57093) probe to DNA digested with Eco RI, Hind III and Bam HI gave the same pattern of bands for genomic and P1 DNA indicating that RAB27B is a single copy gene and that the P1 clones contain this gene
Summary
The Rab subfamily consists of Rab27a and Rab27b. The Rab subfamily consists of Rab27a (previously designated Ram) [5] and Rab27b (previously designated c25KG) [6]. Rab27a was initially cloned from a megakaryocyte library and subsequent studies revealed that it is expressed in haemopoietic-derived cells, melanocytes in skin and eye, lung, pancreas and intestine [5,7,8]. Other tissues such as liver, kidney, brain and muscle show little if any expression of Rab27a. RAB27A was mapped to chromosome 15q21 by fluorescence in situ hybridization and radiation hybrid mapping
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