MOLECULAR-CLONING AND CHARACTERIZATION OF RAB27A AND RAB27B, NOVEL HUMAN RAB PROTEINS SHARED BY MELANOCYTES AND PLATELETS

Rabs are prenylated, membrane-bound proteins involved in vesicular fus ion and trafficking. We isolated the complete cDNAs of two rab isoform s, rab27a and rab27b, from human melanoma cells and melanocytes. Rab27 a is the human homolog of a rat megakaryocyte rab called ram p25. Rab2 7b corresponds to a small GTP-binding protein, c25KG, which was previo usly purified from platelets but whose cDNA had not been cloned. Seque nce comparisons with known rabs indicate that rab27a and rab27b compri se a melanocyte/platelet subfamily within the rab family. In addition, rab27a was expressed in a large variety of cell and tissue types, exc luding brain, and rab27b manifested itself primarily in testis. Bacter ially expressed and purified rab27a and rab27b exhibited GTP-binding a ctivity and can now be used for antibody production and studies of the substrate specificities of geranylgeranyl transferase. In addition, t he expression of rab27a and rab27b in both melanocytes and platelets m akes them candidates for involvement in mouse and human disorders char acterized by the combination of pigment dilution and a platelet storag e pool defect. (C) 1997 Academic Press.