ROLE OF THE SMALL GTPASE RAB7 IN THE LATE ENDOCYTIC PATHWAY

Rab7 is a small GTPase localized to the late endosomal compartment. It s function was investigated by overexpressing dominant negative or con stitutively active mutants in BHK-21 cells. The effects of such overex pression on the internalization and/or degradation of different endocy tic markers and on the morphology of the late endosomal compartment we re analyzed. We observed a marked inhibition of the degradation of I-1 25-low density lipoproteins in cells transfected with the Rab7 dominan t negative mutants while the rate of internalization was not affected. Moreover in these cells there was an accumulation of many small vesic les scattered throughout the cytoplasm. In contrast, overexpression of the activating mutants led to the appearance of atypically large endo cytic structures and caused a dramatic change in the distribution of t he cation-independent mannose 6-phosphate receptor. Our data indicate that the Rab7 protein in mammalian cells is present on a late endosoma l compartment much larger than the compartment labeled by the cation-i ndependent mannose 6-phosphate receptor, Rab7 also appears to play a f undamental role in controlling late endocytic membrane traffic.