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MICAL-like1 mediates epidermal growth factor receptor endocytosis
- Source :
- Molecular Biology of the Cell, Molecular Biology of the Cell, American Society for Cell Biology, 2011, pp.3431-3441, Molecular Biology of the Cell, 2011, 22 (18), pp.3431-3441. ⟨10.1091/mbc.E11-01-0030⟩
- Publication Year :
- 2011
- Publisher :
- HAL CCSD, 2011.
-
Abstract
- MICAL-like1 (MICAL-L1), a Rab13 effector, is associated with late endosomes and regulates epidermal growth factor receptor trafficking. The N-terminal calponin (CH) domain associates with the C-terminal Rab13 binding domain (RBD) of MICAL-L1. The binding of Rab13 to RBD disrupts the CH/RBD interaction and may induce a conformational change in MICAL-L1, promoting its activation.<br />Small GTPase Rabs are required for membrane protein sorting/delivery to precise membrane domains. Rab13 regulates epithelial tight junction assembly and polarized membrane transport. Here we report that Molecule Interacting with CasL (MICAL)-like1 (MICAL-L1) interacts with GTP-Rab13 and shares a similar domain organization with MICAL. MICAL-L1 has a calponin homology (CH), LIM, proline rich and coiled-coil domains. It is associated with late endosomes. Time-lapse video microscopy shows that green fluorescent protein–Rab7 and mcherry-MICAL-L1 are present within vesicles that move rapidly in the cytoplasm. Depletion of MICAL-L1 by short hairpin RNA does not alter the distribution of a late endosome/lysosome-associated protein but affects the trafficking of epidermal growth factor receptor (EGFR). Overexpression of MICAL-L1 leads to the accumulation of EGFR in the late endosomal compartment. In contrast, knocking down MICAL-L1 results in the distribution of internalized EGFR in vesicles spread throughout the cytoplasm and promotes its degradation. Our data suggest that the N-terminal CH domain associates with the C-terminal Rab13 binding domain (RBD) of MICAL-L1. The binding of Rab13 to RBD disrupts the CH/RBD interaction, and may induce a conformational change in MICAL-L1, promoting its activation. Our results provide novel insights into the MICAL-L1/Rab protein complex that can regulate EGFR trafficking at late endocytic pathways.
- Subjects :
- Endosome
Recombinant Fusion Proteins
Endocytic cycle
Video microscopy
Biology
Endocytosis
Cell Line
Mixed Function Oxygenases
03 medical and health sciences
0302 clinical medicine
Dogs
Lysosomal-Associated Membrane Protein 1
Two-Hybrid System Techniques
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Animals
Humans
Molecular Biology
Late endosome
030304 developmental biology
Adaptor Proteins, Signal Transducing
0303 health sciences
Microfilament Proteins
Cell Biology
Articles
Membrane transport
LIM Domain Proteins
Cell biology
Protein Structure, Tertiary
ErbB Receptors
Actin Cytoskeleton
Cytoskeletal Proteins
Protein Transport
Membrane Trafficking
rab GTP-Binding Proteins
Gene Knockdown Techniques
RNA Interference
Rab
Cell Adhesion Molecules
030217 neurology & neurosurgery
Binding domain
Protein Binding
Subjects
Details
- Language :
- English
- ISSN :
- 19394586
- Database :
- OpenAIRE
- Journal :
- Molecular Biology of the Cell, Molecular Biology of the Cell, American Society for Cell Biology, 2011, pp.3431-3441, Molecular Biology of the Cell, 2011, 22 (18), pp.3431-3441. ⟨10.1091/mbc.E11-01-0030⟩
- Accession number :
- edsair.doi.dedup.....636ffcb6984ea38a40c77b36c87bb60e