Synaptic activation modifies microtubules underlying transport of postsynaptic cargo

Synaptic plasticity, the ability of synapses to change in strength, requires alterations in synaptic molecule compositions over time, and synapses undergo selective modifications on stimulation. Molecular motors operate in sorting/transport of neuronal proteins; however, the targeting mechanisms tha...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2009-05, Vol.106 (21), p.8731-8736
Main Authors: Maas, Christoph, Belgardt, Dorthe, Lee, Han Kyu, Heisler, Frank F, Lappe-Siefke, Corinna, Magiera, Maria M, van Dijk, Juliette, Hausrat, Torben J, Janke, Carsten, Kneussel, Matthias
Format: Article
Language:English
Subjects:
Antibodies
Binding sites
Biological Sciences
Biological Transport
Carrier Proteins - metabolism
Cells, Cultured
Freight
Freight transport
Gene expression
Gene expression regulation
Kinesin - metabolism
Membrane Proteins - metabolism
Microtubules
Microtubules - metabolism
Molecules
Neurites
Neurons
Phosphorylation
Physiological regulation
Polyglutamic Acid - metabolism
Proteins
Synapses
Synapses - metabolism
Tubulin - metabolism
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Summary:Synaptic plasticity, the ability of synapses to change in strength, requires alterations in synaptic molecule compositions over time, and synapses undergo selective modifications on stimulation. Molecular motors operate in sorting/transport of neuronal proteins; however, the targeting mechanisms that guide and direct cargo delivery remain elusive. We addressed the impact of synaptic transmission on the regulation of intracellular microtubule (MT)-based transport. We show that increased neuronal activity, as induced through GlyR activity blockade, facilitates tubulin polyglutamylation, a posttranslational modification thought to represent a molecular traffic sign for transport. Also, GlyR activity blockade alters the binding of the MT-associated protein MAP2 to MTs. By using the kinesin (KIF5) and the postsynaptic protein gephyrin as models, we show that such changes of MT tracks are accompanied by reduced motor protein mobility and cargo delivery into neurites. Notably, the observed neurite targeting deficits are prevented on functional depletion or gene expression knockdown of neuronal polyglutamylase. Our data suggest a previously undescribed concept of synaptic transmission regulating MT-dependent cargo delivery.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0812391106