Next Article in Journal
Mechanisms by Which Licochalcone E Exhibits Potent Anti-Inflammatory Properties: Studies with Phorbol Ester-Treated Mouse Skin and Lipopolysaccharide-Stimulated Murine Macrophages
Next Article in Special Issue
Astrocytic Vesicle Mobility in Health and Disease
Previous Article in Journal
Turn-Directed α-β Conformational Transition of α-syn12 Peptide at Different pH Revealed by Unbiased Molecular Dynamics Simulations
Previous Article in Special Issue
New Advances in Urea Transporter UT-A1 Membrane Trafficking
Article

Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality

1
Molecular Biology and Genetics Department, Aarhus University, Aarhus 8000, Denmark
2
Cell Biology Department, Bielefeld University, Bielefeld 33501, Germany
3
Department of Neurosurgery, University Marburg, Marburg 35033, Germany
*
Author to whom correspondence should be addressed.
Current Address: Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Sohngaardsholmsvej 49, Aalborg 9000, Denmark.
Int. J. Mol. Sci. 2013, 14(6), 10908-10925; https://doi.org/10.3390/ijms140610908
Received: 3 April 2013 / Revised: 30 April 2013 / Accepted: 3 May 2013 / Published: 24 May 2013
(This article belongs to the Special Issue Regulation of Membrane Trafficking and Its Potential Implications)
The identification of the mutation causing the phenotype of the amyotrophic lateral sclerosis (ALS) model mouse, wobbler, has linked motor neuron degeneration with retrograde vesicle traffic. The wobbler mutation affects protein stability of Vps54, a ubiquitously expressed vesicle-tethering factor and leads to partial loss of Vps54 function. Moreover, the Vps54 null mutation causes embryonic lethality, which is associated with extensive membrane blebbing in the neural tube and is most likely a consequence of impaired vesicle transport. Investigation of cells derived from wobbler and Vps54 null mutant embryos demonstrates impaired retrograde transport of the Cholera-toxin B subunit to the trans-Golgi network and mis-sorting of mannose-6-phosphate receptors and cargo proteins dependent on retrograde vesicle transport. Endocytosis assays demonstrate no difference between wobbler and wild type cells, indicating that the retrograde vesicle traffic to the trans-Golgi network, but not endocytosis, is affected in Vps54 mutant cells. The results obtained on wobbler cells were extended to test the use of cultured skin fibroblasts from human ALS patients to investigate the retrograde vesicle traffic. Analysis of skin fibroblasts of ALS patients will support the investigation of the critical role of the retrograde vesicle transport in ALS pathogenesis and might yield a diagnostic prospect. View Full-Text
Keywords: Vps54; wobbler; ALS; GARP complex; retrograde vesicle transport Vps54; wobbler; ALS; GARP complex; retrograde vesicle transport
Show Figures

MDPI and ACS Style

Karlsson, P.; Droce, A.; Moser, J.M.; Cuhlmann, S.; Padilla, C.O.; Heimann, P.; Bartsch, J.W.; Füchtbauer, A.; Füchtbauer, E.-M.; Schmitt-John, T. Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality. Int. J. Mol. Sci. 2013, 14, 10908-10925. https://doi.org/10.3390/ijms140610908

AMA Style

Karlsson P, Droce A, Moser JM, Cuhlmann S, Padilla CO, Heimann P, Bartsch JW, Füchtbauer A, Füchtbauer E-M, Schmitt-John T. Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality. International Journal of Molecular Sciences. 2013; 14(6):10908-10925. https://doi.org/10.3390/ijms140610908

Chicago/Turabian Style

Karlsson, Páll, Aida Droce, Jakob M. Moser, Simon Cuhlmann, Carolina O. Padilla, Peter Heimann, Jörg W. Bartsch, Annette Füchtbauer, Ernst-Martin Füchtbauer, and Thomas Schmitt-John. 2013. "Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality" International Journal of Molecular Sciences 14, no. 6: 10908-10925. https://doi.org/10.3390/ijms140610908

Find Other Styles

Article Access Map by Country/Region

1
Only visits after 24 November 2015 are recorded.
Back to TopTop