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Rab4a  -  RAB4A, member RAS oncogene family

Mus musculus

Synonyms: AI848268, Rab4, Ras-related protein Rab-4A
 
 
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Disease relevance of Rab4a

 

High impact information on Rab4a

  • Coexpression of beta2AR with activated Rab4 Q72L caused loss of receptors from heavier endosomes while retaining normal inotropy [3].
  • Rab4 inhibition alone prevented resensitization after isoproterenol-induced in vivo adrenergic desensitization [3].
  • We used mutation and transgenic expression of Rab4, which regulates vesicular transport of heptahelical receptors to plasma membranes, to interrogate in vivo betaAR trafficking and cardiac function [3].
  • In contrast, coexpression of beta2AR with inhibitory Rab4 S27N mimicked isoproterenol-induced receptor redistribution to caveolae, with diminished cardiac inotropy [3].
  • The small GTPase Rab4 is implicated in endocytosis in all cell types, but also plays a specific role in some regulated processes [4].
 

Biological context of Rab4a

  • In this study, we investigated the role of Rab4, a small GTPase-binding protein, and the motor protein KIF3 (kinesin II in mice) in insulin-induced GLUT4 exocytosis in 3T3-L1 adipocytes [5].
  • Thus, the p85alpha protein may play a role in the down-regulation of activated receptors through its temporal control of the GTPase cycles of Rab5 and Rab4 [6].
 

Anatomical context of Rab4a

  • Taken together, these data indicate that (i) insulin signaling stimulates Rab4 activity, the association of Rab4 with kinesin, and the interaction of KIF3 with microtubules and (ii) this process is mediated by insulin-induced PI3-kinase-dependent PKC-lambda activation and participates in GLUT4 exocytosis in 3T3-L1 adipocytes [5].
  • Rab5 and Rab4 are small monomeric GTPases localized on early endosomes and function in vesicle fusion events [6].
  • In adipocyte, this effect results from a blockade of the translocation process because wortmannin inhibited the stimulatory action of insulin on both the Glut 4 movement from the internal compartment to the plasma membranes and the Rab4 departure from the microsomes [7].
  • Enhancement of the Recycling and Activation of beta-Adrenergic Receptor by Rab4 GTPase in Cardiac Myocytes [2].
  • To identify intracellular organelles involved in PrP(Sc) formation, we studied the role of the Ras-related GTP-binding proteins Rab4 and Rab6a in intracellular trafficking of the prion protein and production of PrP(Sc) [8].
 

Associations of Rab4a with chemical compounds

  • Coimmunoprecipitation experiments showed that Rab4, but not Rab5, physically associated with KIF3, and this was confirmed by showing in vitro association using glutathione S-transferase-Rab4 [5].
  • Photoaffinity labeling of Rab4 with [gamma-(32)P]GTP-azidoanilide showed that insulin stimulated Rab4 GTP loading and that this insulin effect was inhibited by pretreatment with the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor LY294002 or expression of dominant-negative protein kinase C-lambda (PKC-lambda) [5].
  • A synthetic peptide corresponding to the Rab4 hypervariable carboxyl-terminal domain inhibits insulin action on glucose transport in rat adipocytes [9].
  • Like insulin, bafilomycin A1 induced the redistribution of GLUT1 and Rab4, but not that of other proteins whose membrane localization has been shown to be insulin-insensitive [10].
  • The small guanosine triphosphate-binding protein Rab4 is involved in insulin-induced GLUT4 translocation and actin filament rearrangement in 3T3-L1 cells [11].
 

Analytical, diagnostic and therapeutic context of Rab4a

  • Analysis by confocal microscopy revealed that, in TC-PTP ko MEFs, activated PDGF beta-receptors colocalized with Rab4a, a marker for rapid recycling [12].
  • A synthetic peptide corresponding to the Rab4 hypervariable carboxyl-terminal domain, Rab4-(191-210), was successfully transferred into rat adipocytes by electroporation and inhibited insulin-stimulated glucose transport by about 50% without affecting the basal transport activity [9].
  • WT Rab4 and Rab4 Q67L microinjection had no effect on either basal or insulin-induced GLUT4 translocation [11].

References

  1. Isolation and sequence determination of cDNA encoding mouse rab 4 and candidate approach for the beige mutation in mice. Ikeda, H., Ikegami, T., Mitsui, T., Sendo, D., Hayasaka, K. Biochem. Mol. Biol. Int. (1996) [Pubmed]
  2. Enhancement of the Recycling and Activation of beta-Adrenergic Receptor by Rab4 GTPase in Cardiac Myocytes. Filipeanu, C.M., Zhou, F., Lam, M.L., Kerut, K.E., Claycomb, W.C., Wu, G. J. Biol. Chem. (2006) [Pubmed]
  3. Regulation of cardiac contractility by Rab4-modulated beta2-adrenergic receptor recycling. Odley, A., Hahn, H.S., Lynch, R.A., Marreez, Y., Osinska, H., Robbins, J., Dorn, G.W. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  4. A FYVE-finger-containing protein, Rabip4, is a Rab4 effector involved in early endosomal traffic. Cormont, M., Mari, M., Galmiche, A., Hofman, P., Le Marchand-Brustel, Y. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  5. Insulin-induced GLUT4 translocation involves protein kinase C-lambda-mediated functional coupling between Rab4 and the motor protein kinesin. Imamura, T., Huang, J., Usui, I., Satoh, H., Bever, J., Olefsky, J.M. Mol. Cell. Biol. (2003) [Pubmed]
  6. The p85alpha subunit of phosphatidylinositol 3'-kinase binds to and stimulates the GTPase activity of Rab proteins. Chamberlain, M.D., Berry, T.R., Pastor, M.C., Anderson, D.H. J. Biol. Chem. (2004) [Pubmed]
  7. Wortmannin inhibits the action of insulin but not that of okadaic acid in skeletal muscle: comparison with fat cells. Le Marchand-Brustel, Y., Gautier, N., Cormont, M., Van Obberghen, E. Endocrinology (1995) [Pubmed]
  8. Stimulation of PrP(C) retrograde transport toward the endoplasmic reticulum increases accumulation of PrP(Sc) in prion-infected cells. Béranger, F., Mangé, A., Goud, B., Lehmann, S. J. Biol. Chem. (2002) [Pubmed]
  9. A synthetic peptide corresponding to the Rab4 hypervariable carboxyl-terminal domain inhibits insulin action on glucose transport in rat adipocytes. Shibata, H., Omata, W., Suzuki, Y., Tanaka, S., Kojima, I. J. Biol. Chem. (1996) [Pubmed]
  10. Arrest of endosome acidification by bafilomycin A1 mimics insulin action on GLUT4 translocation in 3T3-L1 adipocytes. Chinni, S.R., Shisheva, A. Biochem. J. (1999) [Pubmed]
  11. The small guanosine triphosphate-binding protein Rab4 is involved in insulin-induced GLUT4 translocation and actin filament rearrangement in 3T3-L1 cells. Vollenweider, P., Martin, S.S., Haruta, T., Morris, A.J., Nelson, J.G., Cormont, M., Le Marchand-Brustel, Y., Rose, D.W., Olefsky, J.M. Endocrinology (1997) [Pubmed]
  12. Loss of T-Cell Protein Tyrosine Phosphatase Induces Recycling of the Platelet-derived Growth Factor (PDGF) beta-Receptor but Not the PDGF {alpha}-Receptor. Karlsson, S., Kowanetz, K., Sandin, A., Persson, C., Ostman, A., Heldin, C.H., Hellberg, C. Mol. Biol. Cell (2006) [Pubmed]
 
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