Disease relevance of Rab5

• In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphatase Ypt1p, which associated with cytoplasmic alphaSyn inclusions [1].

High impact information on Rab5

• Disruption of endocytosis by dominant negative dynamin or Rab5 prevents Smo internalization [2].
• Mutations in a second class of genes, the neoplastic tumor-suppressor genes, disrupt proteins that function either as scaffolds at cell-cell junctions (scribble, discs large, lgl) or as components of the endocytic pathway (avalanche, rab5, ESCRT components) [3].
• Protein accumulation results from a failure in endosomal entry and progression towards lysosomal degradation; these and other avl phenotypes are also detected in Rab5 null mutant cells [4].
• We demonstrate that the small GTPase Rab5 is required for endosome integrity in the presynaptic terminal [5].
• Impaired Rab5 function affects endo- and exocytosis rates and decreases the evoked neurotransmitter release probability [5].

Anatomical context of Rab5

• These enlarged endosomes are positive for Rab5 and Hrs, a protein involved in trafficking into the degradative pathway [6].
• Finally, blocking the N transportation from the plasma membrane to the late-endosome by a dominant-negative form of Rab5 inhibited the Dx-mediated activation of N signaling, suggesting that the accumulation of N in the late-endosome was required for the Dx-mediated Su(H)-independent N signaling [7].
• By contrast, GPI-AP and fluid-phase endocytosis are quantitatively unaffected at the restrictive temperature in shits hemocytes, demonstrating a constitutive dDyn and Rab5-independent endocytic pathway in Drosophila [8].
• Analysis of mutations in beta(Heavy)-spectrin, the Drosophila brush border spectrin, reveals that this protein is necessary for the maintenance of Rab5 endosomes in the midgut [9].
• These novel interactions between the microtubule-binding Hook1 and the large family of Rab GTPases also suggest a link between CLN3 function, microtubule cytoskeleton and endocytic membrane trafficking [10].

Associations of Rab5 with chemical compounds

• Absence of Sprint, a receptor-recruited, Ras-activated Rab5 guanine exchange factor, gives related defects [11].

Other interactions of Rab5

• Second, N at the plasma membrane was relocated to the SAC/AJs by Dynamin- and Rab5-dependent transcytosis; this step required the O-fut1 function [12].
• This C-terminal domain was found to bind a subset of Rab GTPases, especially Rab11, in a GTP-dependent manner [13].
• Epistasis tests indicate that beta(Heavy)-spectrin is required during endocytosis after Dynamin and before Rab5-mediated endosome activities [9].
• As a consequence, an apical H+ V-ATPase that is probably responsible for lumenal acidification is lost both from the brush border and Rab5 endosomes [9].

References