Structural determinants allowing endolysosomal sorting and degradation of endosomal GTPases
| Autor: | Mónica Herrera, Dolores Pérez-Sala, Ruth A. Valero, Clara L. Oeste, Irene Ramos, Patricia Boya, Konstantinos Stamatakis |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Human lysosomes
Endosome RHOB Molecular Sequence Data GTPase macromolecular substances Endosomes Biology Protein degradation medicine.disease_cause Biochemistry GTP Phosphohydrolases Amino acid sequence rhoB GTP-binding protein Palmitoylation Structural Biology Molecular sequence data Protein targeting RhoB GTP-Binding Protein Genetics medicine Animals Humans Amino Acid Sequence rhoB GTP-Binding Protein Molecular Biology Late endosome Endosomal Sorting Complexes Required for Transport Cell Biology GTP phosphohydrolases Cell biology Endosomal sorting complexes required for transport Lysosomes |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| ISSN: | 1600-0854 |
| Popis: | Rapid control of protein degradation is usually achieved through the ubiquitin-proteasome pathway. We recently found that the short-lived GTPase RhoB is degraded in lysosomes. Moreover, the fusion of the RhoB C-terminal sequence CINCCKVL, containing the isoprenylation and palmitoylation sites, to other proteins directs their sorting into multivesicular bodies (MVBs) and rapid lysosomal degradation. Here, we show that this process is highly specific for RhoB. Alteration of late endosome lipid dynamics produced the accumulation of RhoB, but not of other endosomal GTPases, including Rab5, Rab7, Rab9 or Rab11, into enlarged MVB. Other isoprenylated and bipalmitoylated GTPases, such as H-Ras, Rap2A, Rap2B and TC10, were not accumulated into MVB and were stable. Remarkably, although TC10, which is highly homologous to RhoB, was stable, a sequence derived from its C-terminus (CINCCLIT) elicited MVB sorting and degradation of a green fluorescent protein (GFP)-chimeric protein. This led us to identify a cluster of basic amino acids (KKH) in the TC10 hypervariable region, constituting a secondary signal potentially involved in electrostatic interactions with membrane lipids. Mutation of this cluster allowed TC10 MVB sorting and degradation, whereas inserting it into RhoB hypervariable region rescued this protein from its lysosomal degradation pathway. These findings define a highly specific structural module for entering the MVB pathway and rapid lysosomal degradation. This work was supported by grants from MiCInn SAF2009-11642 and SAF2009-08086 and by RETICS RIRAAF from ISCIII, RD07/0064/0007 and PIE201020E031 from CSIC. C. L. O. has been supported by a JAE Intro fellowship from CSIC. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|