Ligand-dependent and -independent transforming growth factor-beta receptor recycling regulated by clathrin-mediated endocytosis and Rab11

Proteins in the transforming growth factor-beta (TGF-beta) family recognize transmembrane serine/threonine kinases known as type I and type II receptors. Binding of TGF-beta to receptors results in receptor down-regulation and signaling. Whereas previous work has focused on activities controlling TG...

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Bibliographic Details
Published in:Molecular biology of the cell 2004-09, Vol.15 (9), p.4166-4178
Main Authors: Mitchell, Hugh, Choudhury, Amit, Pagano, Richard E, Leof, Edward B
Format: Article
Language:English
Subjects:
Animals
Biological Transport, Active
Cell Line
Clathrin - metabolism
Endocytosis
Granulocyte-Macrophage Colony-Stimulating Factor - metabolism
Ligands
Mink
Models, Biological
Monensin - pharmacology
rab GTP-Binding Proteins - genetics
rab GTP-Binding Proteins - metabolism
rab4 GTP-Binding Proteins - genetics
rab4 GTP-Binding Proteins - metabolism
Receptors, Transforming Growth Factor beta - genetics
Receptors, Transforming Growth Factor beta - metabolism
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
RNA Interference
Transforming Growth Factor beta - metabolism
Transforming Growth Factor beta1
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Summary:Proteins in the transforming growth factor-beta (TGF-beta) family recognize transmembrane serine/threonine kinases known as type I and type II receptors. Binding of TGF-beta to receptors results in receptor down-regulation and signaling. Whereas previous work has focused on activities controlling TGF-beta signaling, more recent studies have begun to address the trafficking properties of TGF-beta receptors. In this report, it is shown that receptors undergo recycling both in the presence and absence of ligand activation, with the rates of internalization and recycling being unaffected by ligand binding. Recycling occurs as receptors are most likely internalized through clathrin-coated pits, and then returned to the plasma membrane via a rab11-dependent, rab4-independent mechanism. Together, the results suggest a mechanism wherein activated TGF-beta receptors are directed to a distinct endocytic pathway for down-regulation and clathrin-dependent degradation after one or more rounds of recycling.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E04-03-0245