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Annexin A8 regulates late endosome organization and function.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2008 Dec; Vol. 19 (12), pp. 5267-78. Date of Electronic Publication: 2008 Oct 15. - Publication Year :
- 2008
-
Abstract
- Different classes of endosomes exhibit a characteristic intracellular steady-state distribution governed by interactions with the cytoskeleton. Late endosomes, organelles of the degradative lysosomal route, seem to require associated actin filaments for proper localization and function. We show here that the F-actin and phospholipid binding protein annexin A8 is associated specifically with late endosomes. Altering intracellular annexin A8 levels drastically affected the morphology and intracellular distribution of late endosomes. Trafficking through the degradative pathway was delayed in the absence of annexin A8, resulting in attenuated ligand-induced degradation of the epidermal growth factor receptor and prolonged epidermal growth factor-induced activation of mitogen-activated protein kinase. Depletion of annexin A8 reduced the association of late endosomal membranes with actin filaments. These results indicate that the defective cargo transport through the late endocytic pathway and the imbalanced signaling of activated receptors observed in the absence of annexin A8 results from the disturbed association of late endosomal membranes with the actin network, resulting in impaired actin-based late endosome motility.
- Subjects :
- Actins metabolism
Animals
Annexins genetics
Cell Fractionation
Cytoskeleton metabolism
Cytoskeleton ultrastructure
Endosomes ultrastructure
Enzyme Activation
Epidermal Growth Factor metabolism
ErbB Receptors metabolism
Extracellular Signal-Regulated MAP Kinases metabolism
HeLa Cells
Humans
Intracellular Membranes metabolism
Lysosomal Membrane Proteins genetics
Lysosomal Membrane Proteins metabolism
Lysosomes metabolism
Neoplasm Proteins genetics
Neoplasm Proteins metabolism
Protein Transport physiology
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Annexins metabolism
Endocytosis physiology
Endosomes metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1939-4586
- Volume :
- 19
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 18923148
- Full Text :
- https://doi.org/10.1091/mbc.E08-04-0383