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

Karlsson P, Droce A, Moser JM, Cuhlmann S, Padilla CO, Heimann P, Bartsch JW, Fuchtbauer A, Fuchtbauer E-M, Schmitt-John T (2013)
International Journal Of Molecular Sciences 14(6): 10908-10925.

Journal Article | Published | English

No fulltext has been uploaded

Author
; ; ; ; ; ; ; ; ;
Abstract
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.
Publishing Year
ISSN
eISSN
PUB-ID

Cite this

Karlsson P, Droce A, Moser JM, et al. 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.
Karlsson, P., Droce, A., Moser, J. M., Cuhlmann, S., Padilla, C. O., Heimann, P., Bartsch, J. W., et al. (2013). Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality. International Journal Of Molecular Sciences, 14(6), 10908-10925.
Karlsson, P., Droce, A., Moser, J. M., Cuhlmann, S., Padilla, C. O., Heimann, P., Bartsch, J. W., Fuchtbauer, A., Fuchtbauer, E. - M., and Schmitt-John, T. (2013). Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality. International Journal Of Molecular Sciences 14, 10908-10925.
Karlsson, P., et al., 2013. Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality. International Journal Of Molecular Sciences, 14(6), p 10908-10925.
P. Karlsson, et al., “Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality”, International Journal Of Molecular Sciences, vol. 14, 2013, pp. 10908-10925.
Karlsson, P., Droce, A., Moser, J.M., Cuhlmann, S., Padilla, C.O., Heimann, P., Bartsch, J.W., Fuchtbauer, A., Fuchtbauer, 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. 14, 10908-10925 (2013).
Karlsson, Pall, Droce, Aida, Moser, Jakob M., Cuhlmann, Simon, Padilla, Carolina Ortiz, Heimann, Peter, Bartsch, Joerg W., Fuchtbauer, Annette, Fuchtbauer, Ernst-Martin, and Schmitt-John, Thomas. “Loss of Vps54 Function Leads to Vesicle Traffic Impairment, Protein Mis-Sorting and Embryonic Lethality”. International Journal Of Molecular Sciences 14.6 (2013): 10908-10925.
This data publication is cited in the following publications:
This publication cites the following data publications:

8 Citations in Europe PMC

Data provided by Europe PubMed Central.

Inflammation and neuronal death in the motor cortex of the wobbler mouse, an ALS animal model.
Dahlke C, Saberi D, Ott B, Brand-Saberi B, Schmitt-John T, Theiss C., J Neuroinflammation 12(), 2015
PMID: 26597538
VPS54 and the wobbler mouse.
Schmitt-John T., Front Neurosci 9(), 2015
PMID: 26539077
Post-Golgi anterograde transport requires GARP-dependent endosome-to-TGN retrograde transport.
Hirata T, Fujita M, Nakamura S, Gotoh K, Motooka D, Murakami Y, Maeda Y, Kinoshita T., Mol. Biol. Cell 26(17), 2015
PMID: 26157166
Implementation of a manual for working with wobbler mice and criteria for discontinuation of the experiment.
Ott B, Dahlke C, Meller K, Napirei M, Schmitt-John T, Brand-Saberi B, Theiss C, Saberi D., Ann. Anat. 200(), 2015
PMID: 25929815
Comparative profiling of the sperm proteome.
Holland A, Ohlendieck K., Proteomics 15(4), 2015
PMID: 24909132
TPC1 has two variant isoforms, and their removal has different effects on endo-lysosomal functions compared to loss of TPC2.
Ruas M, Chuang KT, Davis LC, Al-Douri A, Tynan PW, Tunn R, Teboul L, Galione A, Parrington J., Mol. Cell. Biol. 34(21), 2014
PMID: 25135478
Intricate effects of primary motor neuronopathy on contractile proteins and metabolic muscle enzymes as revealed by label-free mass spectrometry.
Holland A, Schmitt-John T, Dowling P, Meleady P, Henry M, Clynes M, Ohlendieck K., Biosci. Rep. 34(4), 2014
PMID: 24895011

30 References

Data provided by Europe PubMed Central.


Nagy A., Gertsenstein M., Vintersten K., Behringer R., 2003
Trafficking of Na,K-ATPase fused to enhanced green fluorescent protein is mediated by protein kinase A or C.
Kristensen B, Birkelund S, Jorgensen PL., J. Membr. Biol. 191(1), 2003
PMID: 12532274
Occurrence of an anomalous endocytic compartment in fibroblasts from Sandhoff disease patients.
Tancini B, Magini A, Latterini L, Urbanelli L, Ciccarone V, Elisei F, Emiliani C., Mol. Cell. Biochem. 335(1-2), 2010
PMID: 19823769
Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein.
Andersen OM, Reiche J, Schmidt V, Gotthardt M, Spoelgen R, Behlke J, von Arnim CA, Breiderhoff T, Jansen P, Wu X, Bales KR, Cappai R, Masters CL, Gliemann J, Mufson EJ, Hyman BT, Paul SM, Nykjaer A, Willnow TE., Proc. Natl. Acad. Sci. U.S.A. 102(38), 2005
PMID: 16174740

Export

0 Marked Publications

Open Data PUB

Web of Science

View record in Web of Science®

Sources

PMID: 23708095
PubMed | Europe PMC

Search this title in

Google Scholar