Phosphorylation of FEZ1 by Microtubule Affinity Regulating Kinases regulates its function in presynaptic protein trafficking
2016 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Phosphorylation of FEZ1 by Microtubule Affinity Regulating Kinases regulates its function in presynaptic protein trafficking
Butkevich, E.; Haertig, W.; Nikolov, M. ; Erck, C.; Grosche, J.; Urlaub, H. & Schmidt, C. et al. (2016)
Scientific Reports, 6 art. 26965. DOI: https://doi.org/10.1038/srep26965
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Details
- Authors
- Butkevich, Eugenia; Haertig, Wolfgang; Nikolov, Miroslav ; Erck, Christian; Grosche, Jens; Urlaub, Henning ; Schmidt, Christoph ; Klopfenstein, Dieter R. ; Chua, John Jia En
- Abstract
- Adapters bind motor proteins to cargoes and therefore play essential roles in Kinesin-1 mediated intracellular transport. The regulatory mechanisms governing adapter functions and the spectrum of cargoes recognized by individual adapters remain poorly defined. Here, we show that cargoes transported by the Kinesin-1 adapter FEZ1 are enriched for presynaptic components and identify that specific phosphorylation of FEZ1 at its serine 58 regulatory site is mediated by microtubule affinity-regulating kinases (MARK/PAR-1). Loss of MARK/PAR-1 impairs axonal transport, with adapter and cargo abnormally co-aggregating in neuronal cell bodies and axons. Presynaptic specializations are markedly reduced and distorted in FEZ1 and MARK/PAR-1 mutants. Strikingly, abnormal co-aggregates of unphosphorylated FEZ1, Kinesin-1 and its putative cargoes are present in brains of transgenic mice modelling aspects of Alzheimer's disease, a neurodegenerative disorder exhibiting impaired axonal transport and altered MARK activity. Our findings suggest that perturbed FEZ1-mediated synaptic delivery of proteins arising from abnormal signalling potentially contributes to the process of neurodegeneration.
- Issue Date
- 2016
- Publisher
- Nature Publishing Group
- Journal
- Scientific Reports
- Organization
- Fakultät für Physik
- ISSN
- 2045-2322