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 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.
Zentrum für Molekulare Neurobiologie Hamburg, Universität Hamburg, Hamburg, Germany.
Christoph
C
Maas
Dorthe
D
Belgardt
Han Kyu
HK
Lee
Frank F
FF
Heisler
Corinna
C
Lappe-Siefke
Maria M
MM
Magiera
Juliette
J
van Dijk
Torben J
TJ
Hausrat
Carsten
C
Janke
Matthias
M
Kneussel
D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D016547:Kinesins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D011099:Polyglutamic Acid / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D014404:Tubulin / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D014404:Tubulin; C073441:gephyrin; D011099:Polyglutamic Acid; D016547:Kinesins