CLONING OF A BRAIN-TYPE ISOFORM OF HUMAN RAB GDI AND ITS EXPRESSION IN HUMAN NEUROBLASTOMA CELL-LINES AND TUMOR SPECIMENS

Rab proteins, a family of Ras-related small GTP-binding proteins, play a key role in regulating intracellular vesicle trafficking, Rab GDP d issociation inhibitor (GDI(3)) forms a soluble complex with Rab protei ns and thereby prevents the exchange of GDP for GTP, Recently, two iso forms of Rab GDI cDNA were isolated from rats and mice. In this study, we have isolated a brain-type isoform of human Rab GDI cDNA and exami ned its expression in neuroblastoma. We tentatively designate it as hu man Rab GDI alpha (hu GDI alpha) and another human Rab GDI, as human R ab GDI beta (hu GDI beta), Hu GDI alpha cDNA encodes a protein of 447 amino acids with a deduced molecular weight of 50,200. Northern blot a nalysis revealed that hu GDI alpha gene is expressed abundantly in the brain but much less in other tissues, while hu GDI beta gene is ubiqu itously expressed. All human neuroblastoma cell lines and tumor specim ens examined express hu GDI alpha gene to various extents, while a hum an T cell leukemia cell line, MOLT3, does not. The levels of both hu G DI cu and beta mRNA were constant in a human neuroblastoma cell line, NB1, during its neuronal differentiation, while Rab3A and neurofilamen t-L gene expression and the number of neurosecretory granules were ele vated at this condition, These results suggest that hu GDI alpha gene expression is not related to the differentiation state of neuronal cel ls.