Rab4 affects both recycling and degradative endosomal trafficking
| Autor: | Vera Roberti, Anna Bielli, Frances J. Drummond, Mariarosaria Santillo, Cecilia Bucci, Silvia Mora, Mary W. McCaffrey, Giuseppina Cantalupo |
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| Přispěvatelé: | MCCAFFREY M., W, Bielli, A, Cantalupo, G, Mora, S, Roberti, V, Santillo, M, Drummond, F, Bucci, Cecilia, Mccaffrey, Mary W, Bielli, Anna, Cantalupo, Giuseppina, Mora, Silvia, Roberti, Vera, Santillo, Mariarosaria, Drummond, France |
| Rok vydání: | 2001 |
| Předmět: |
Endosome
media_common.quotation_subject Endocytic cycle Mutant Biophysics Gene Expression Low density lipoprotein Endosomes Membrane trafficking GTPase Biology Ligands Transfection Endocytosis Microtubules Biochemistry Iodine Radioisotopes Structural Biology Epidermal growth factor Receptors Transferrin Genetics Humans Internalization Molecular Biology Genes Dominant rab5 GTP-Binding Proteins media_common chemistry.chemical_classification Endocytosi rab4 GTP-Binding Proteins Transferrin rab7 GTP-Binding Proteins Cell Biology Cell Compartmentation Cell biology Lipoproteins LDL Protein Transport Biophysic chemistry rab GTP-Binding Proteins Mutagenesis Site-Directed Rab GTPase HeLa Cells |
| Zdroj: | FEBS Letters. 495:21-30 |
| ISSN: | 0014-5793 |
| DOI: | 10.1016/s0014-5793(01)02359-6 |
| Popis: | The small GTPases Rab4, Rab5 and Rab7 are endosomal proteins which play important roles in the regulation of various stages of endosomal trafficking. Rab4 and Rab5 have both been localized to early endosomes and have been shown to control recycling and endosomal fusion, respectively. Rab7, a marker of the late endosomal compartment, is involved in the regulation of the late endocytic pathway. Here, we compare the role of Rab4, Rab5 and Rab7 in early and late endosomal trafficking in HeLa cells monitoring ligand uptake, recycling and degradation. Expression of the Rab4 dominant negative mutant (Rab4AS22N) leads to a significant reduction in both recycling and degradation while, as expected, Rab7 mutants exclusively affect epidermal growth factor (EGF) and low density lipoprotein degradation. As also expected, expression of the dominant negative Rab5 mutant perturbs internalization kinetics and affects both recycling and degradation. Expression of Rab4WT and dominant positive mutant (Rab4AQ67L) changes dramatically the morphology of the transferrin compartment leading to the formation of membrane tubules. These transferrin positive tubules display swellings (varicosities) some of which are positive for early endosomal antigen-1 and contain EGF. We propose that the Rab4GTPase is important for the function of the early sorting endosomal compartment, affecting trafficking along both recycling and degradative pathways. |
| Databáze: | OpenAIRE |
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