Abstract |
Mutations in the motor protein Myosin Vb (Myo5B) or the soluble NSF attachment protein receptor Syntaxin 3 (Stx3) disturb epithelial polarity and cause microvillus inclusion disease (MVID), a lethal hereditary enteropathy affecting neonates. To understand the molecular mechanism of Myo5B and Stx3 interplay, we used genome editing to introduce a defined Myo5B patient mutation in a human epithelial cell line. Our results demonstrate a selective role of Myo5B and Stx3 for apical cargo exocytosis in polarized epithelial cells. Apical exocytosis of NHE3, CFTR ( cystic fibrosis transmembrane conductance regulator), and GLUT5 required an interaction cascade of Rab11, Myo5B, Slp4a, Munc18-2, and Vamp7 with Stx3, which cooperate in the final steps of this selective apical traffic pathway. The brush border enzymes DPPIV and sucrase- isomaltase still correctly localize at the apical plasma membrane independent of this pathway. Hence, our work demonstrates how Myo5B, Stx3, Slp4a, Vamp7, Munc18-2, and Rab8/11 cooperate during selective apical cargo trafficking and exocytosis in epithelial cells and thereby provides further insight into MVID pathophysiology.
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Authors | Georg F Vogel, Katharina M C Klee, Andreas R Janecke, Thomas Müller, Michael W Hess, Lukas A Huber |
Journal | The Journal of cell biology
(J Cell Biol)
Vol. 211
Issue 3
Pg. 587-604
(Nov 09 2015)
ISSN: 1540-8140 [Electronic] United States |
PMID | 26553929
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2015 Vogel et al. |
Chemical References |
- Glucose Transporter Type 5
- MYO5B protein, human
- Munc18 Proteins
- Qa-SNARE Proteins
- R-SNARE Proteins
- SLC2A5 protein, human
- SLC9A3 protein, human
- SYTL4 protein, human
- Sodium-Hydrogen Exchanger 3
- Sodium-Hydrogen Exchangers
- VAMP7 protein, human
- Vesicular Transport Proteins
- Cystic Fibrosis Transmembrane Conductance Regulator
- Myosin Type V
- rab11 protein
- Myosin Heavy Chains
- rab GTP-Binding Proteins
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Topics |
- Caco-2 Cells
- Cell Line
- Cell Line, Tumor
- Cell Membrane
(metabolism)
- Cell Polarity
(physiology)
- Cystic Fibrosis Transmembrane Conductance Regulator
(metabolism)
- Epithelial Cells
(metabolism, physiology)
- Exocytosis
(physiology)
- Glucose Transporter Type 5
(metabolism)
- HEK293 Cells
- Humans
- Malabsorption Syndromes
(metabolism)
- Microvilli
(metabolism, pathology)
- Mucolipidoses
(metabolism)
- Munc18 Proteins
(metabolism)
- Mutation
(physiology)
- Myosin Heavy Chains
(metabolism)
- Myosin Type V
(metabolism)
- Qa-SNARE Proteins
(metabolism)
- R-SNARE Proteins
(metabolism)
- Signal Transduction
(physiology)
- Sodium-Hydrogen Exchanger 3
- Sodium-Hydrogen Exchangers
(metabolism)
- Vesicular Transport Proteins
(metabolism)
- rab GTP-Binding Proteins
(metabolism)
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