Disease relevance of Rab7

• Downregulation of small GTPase Rab7 impairs osteoclast polarization and bone resorption [1].
• Moreover, strategies aimed at controlling Rab7 activity might be useful for the treatment of neurodegenerative diseases [2].
• Because mutations of Rab7 are found in patients suffering from hereditary polyneuropathies, dysfunction of Rab7 might contribute to neurodegenerative conditions by affecting the trafficking of neurotrophins [2].

High impact information on Rab7

• We demonstrate further that Rab7 colocalizes with Rac1 at the fusion zone of the ruffled border in bone-resorbing osteoclasts [3].
• Possible role of direct Rac1-Rab7 interaction in ruffled border formation of osteoclasts [3].
• As compared with early vesicles, late vesicles had reduced association with receptor, Rab4, and kinesin I but were highly associated with dynein, Rab7, dynactin, and KIF3A [4].
• TNF-alpha stimulated the colocalization of GD3 with early and late endosomal markers, Rab 5 and Rab 7, whereas perturbation of plasma membrane cholesterol or actin cytoskeleton or inhibition of glucosylceramide synthase prevented the trafficking of GD3 to mitochondria [5].
• Here we show that Rab7, a small GTPase that is associated with late endosomes, is highly expressed and is predominantly localized at the ruffled border in bone-resorbing osteoclasts [1].

Anatomical context of Rab7

• The decreased expression of Rab7 in cultured osteoclasts by antisense oligodeoxynucleotides disrupted the polarization of the osteoclasts and the targeting of vesicles to the ruffled border [1].
• Because Rac1 is known to control the actin cytoskeleton through its effectors, the Rab7-Rac1 interaction may mediate late endosomal transport between microtubules and microfilaments enabling endosomal vesicles to switch tracks and may thus also regulate ruffled border formation in osteoclasts [3].
• Internalized SP-A cannot be resecreted rapidly to plasma membrane, and lipid is not transported toward late endosomes (Rab7- and M6PR-positive) or lamellar bodies (CD63- and 3C9-positive) [6].
• Here we report that depletion of intracellular mevalonate by lovastatin in FRTL-5 thyroid cells specifically resulted in a four-fold increase of Rab5 and Rab7 protein levels [7].
• Our studies show that the endosomal GTPase Rab7 controls the endosomal trafficking and neurite outgrowth signaling of TrkA [2].

Other interactions of Rab7

• Identification of Rab GTPases 4, 5, 18, and 21 (associated with early endosomes); Rab7 (late endosomes); and Rab11 and Rab25 (recycling endosomes) indicate that a substantial fraction of intracellular AQP2 is present in endosomal compartments [8].

Analytical, diagnostic and therapeutic context of Rab7

• The effects of IL-4 and IL-13 were accompanied by redistribution of the small GTPases Rab5b and Rab7, as shown by confocal immunofluorescence studies [9].

References