Please use this identifier to cite or link to this item: https://doi.org/10.1038/srep26965
Title: Phosphorylation of FEZ1 by Microtubule Affinity Regulating Kinases regulates its function in presynaptic protein trafficking
Authors: Butkevich, Eugenia
Haertig, Wolfgang
Nikolov, Miroslav
Erck, Christian
Grosche, Jens
Urlaub, Henning
Schmidt, Christoph F
Klopfenstein, Dieter R
Chua, John Jia En 
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
FAST AXONAL-TRANSPORT
ALZHEIMERS-DISEASE
CAENORHABDITIS-ELEGANS
INTERACTING PROTEIN
KINESIN-1 ADAPTER
C-ELEGANS
IDENTIFICATION
OUTGROWTH
POLARITY
VESICLE
Issue Date: 1-Jun-2016
Publisher: NATURE PUBLISHING GROUP
Citation: Butkevich, Eugenia, Haertig, Wolfgang, Nikolov, Miroslav, Erck, Christian, Grosche, Jens, Urlaub, Henning, Schmidt, Christoph F, Klopfenstein, Dieter R, Chua, John Jia En (2016-06-01). Phosphorylation of FEZ1 by Microtubule Affinity Regulating Kinases regulates its function in presynaptic protein trafficking. SCIENTIFIC REPORTS 6 (1). ScholarBank@NUS Repository. https://doi.org/10.1038/srep26965
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 Alzheimerâ 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.
Source Title: SCIENTIFIC REPORTS
URI: https://scholarbank.nus.edu.sg/handle/10635/168495
ISSN: 2045-2322,2045-2322
DOI: 10.1038/srep26965
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