Rab9 functions in transport between late endosomes and the trans Golgi network.

Abstract

Rab proteins represent a large family of ras‐like GTPases that regulate distinct vesicular transport events at the level of membrane targeting and/or fusion. We report here the primary sequence, subcellular localization and functional activity of a new member of the rab protein family, rab9. The majority of rab9 appears to be located on the surface of late endosomes. Rab9, purified from Escherichia coli strains expressing this protein, could be prenylated in vitro in the presence of cytosolic proteins and geranylgeranyl diphosphate. In vitro‐prenylated rab9 protein, but not C‐terminally truncated rab9, stimulated the transport of mannose 6‐phosphate receptors from late endosomes to the trans Golgi network in a cell‐free system that reconstitutes this transport step. Rab7, a related rab protein that is also localized to late endosomes, was inactive in the in vitro transport assay, despite its efficient prenylation and capacity to bind and hydrolyze GTP. These results strongly suggest that rab9 functions in the transport of mannose 6‐phosphate receptors between late endosomes and the trans Golgi network. Moreover, our results confirm the observation that a given organelle may bear multiple rab proteins with different biological functions.

The Oxysterol-binding Protein Homologue ORP1L Interacts with Rab7 and Alters Functional Properties of Late Endocytic Compartments

“…In the present study, we show that in HeLa cells the OSBP homologue ORP1L localizes on late endocytic compartments and its distribution overlaps largely with those of Lamp-1, the small GTPase Rab7, a central regulator of late endosomal membrane trafficking events, and Rab9, a GTPase with a key role in the route from late endosomes to the trans-Golgi (Lombardi et al, 1993;Carroll et al, 2001). The finding that ORP1L overexpression induced clustering of LE/lysosomes prompted us to test whether ORP1L interacts with the late endosomal small GTPases.…”

The vacuolar ATPase proton pump is required for the cytotoxicity of Bacillus anthracis lethal toxin

“…But it indicates that the acidic organelle where LF becomes competent to cross the membrane is a late endosomal compartment. The actual translocation of LF into the cytosol could take place in late endosomes themselves as well as in the trans Golgi compartment which is dynamically linked to late endosomes via a membrane trafficking pathway controlled by rab9 [29,30]. This is at variance from what was found before with diphtheria toxin, which is the best characterized protein toxin requiring a transmembrane pH gradient to translocate its catalytic subunit into the cell cytosol.…”

A Phosphorylated Cytoplasmic Autoantigen, GW182, Associates with a Unique Population of Human mRNAs within Novel Cytoplasmic Speckles

“…Brefeldin, a fungal toxin known to rapidly dissociate the Golgi complex (Orci et al, 1991) did not affect the morphology, size, or number of these structures (our unpublished results). The staining did not colocalize with clathrin-coated vesicles (Figure 1C), with the early endosomal protein EEA1 ( Figure 1D; Mu et al, 1995;Selak et al, 1999;Lawe et al, 2000), with the late endosomal protein rab9 (Lombardi et al, 1993; Figure 1E), with the peroxisome membrane protein PMP70 ( Figure 1F; Kamijo et al, 1990), with LAMP1 ( Figure 1G), a lysosome marker (Fukuda et al, 1988), or with caveolin (our unpublished results; Conrad et al, 1995;Song et al, 1995). Last, antibodies to ubiquitin ligases, cullin-1 (Kipreos et al, 1996;Lisztwan et al, 1998) and p19 Skp1 (Zhang et al, 1995;Bai et al, 1996;Connelly and Hieter, 1996), members of the SCF family of ubiquitin ligases (for Skp1, Cdc53/Cullin, F-box receptor; Feldman et al, 1997;Skowyra et al, 1997), did not colocalize with these structures either (our unpublished results).…”