Rab-interacting lysosomal protein (RILP): the Rab7 effector required for transport to lysosomes

Rab7 is a small GTPase that controls transport to endocytic degradative com partments. Here we report the identification of a novel 45 kDa protein that specifically binds Rab7GTP at its C-terminus. This protein contains a doma in comprising two coiled-coil regions typical of myosin-like proteins and i s found mainly in the cytosol. We named it RILP (Rab-interacting lysosomal protein) since it can be recruited efficiently on late endosomal and lysoso mal membranes by Rab7GTP. RILP-C33 (a truncated form of the protein lacking the N-terminal half) strongly inhibits epidermal growth factor and low-den sity lipoprotein degradation, and causes dispersion of lysosomes similarly to Rab7 dominant-negative mutants. More importantly, expression of RILP rev erses/prevents the effects of Rab7 dominant-negative mutants. All these dat a are consistent with a model in which RILP represents a downstream effecto r for Rab7 and both proteins act together in the regulation of late endocyt ic traffic.