Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity.
Dendritic spines are the major sites of excitatory synaptic input, and their morphological changes have been linked to learning and memory processes. Here, we report that growing microtubule plus ends decorated by the microtubule tip-tracking protein EB3 enter spines and can modulate spine morphology. We describe p140Cap/SNIP, a regulator of Src tyrosine kinase, as an EB3 interacting partner that is predominantly localized to spines and enriched in the postsynaptic density. Inhibition of microtubule dynamics, or knockdown of either EB3 or p140Cap, modulates spine shape via regulation of the actin cytoskeleton. Fluorescence recovery after photobleaching revealed that EB3-binding is required for p140Cap accumulation within spines. In addition, we found that p140Cap interacts with Src substrate and F-actin-binding protein cortactin. We propose that EB3-labeled growing microtubule ends regulate the localization of p140Cap, control cortactin function, and modulate actin dynamics within dendritic spines, thus linking dynamic microtubules to spine changes and synaptic plasticity.
Jaworski
Jacek
J
Department of Neuroscience, Erasmus Medical Center, 3015 GE, Rotterdam, The Netherlands.
Kapitein
Lukas C
LC
Gouveia
Susana Montenegro
SM
Dortland
Bjorn R
BR
Wulf
Phebe S
PS
Grigoriev
Ilya
I
Camera
Paola
P
Spangler
Samantha A
SA
Di Stefano
Paola
P
Demmers
Jeroen
J
Krugers
Harm
H
Defilippi
Paola
P
Akhmanova
Anna
A
Hoogenraad
Casper C
CC
D000199:Actins / Q000378:metabolism; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051356:Cortactin / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D006367:HeLa Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D050257:Tubulin Modulators / Q000494:pharmacology
D000199:Actins; D033942:Adaptor Proteins, Vesicular Transport; D051356:Cortactin; C534832:Mapre3 protein, rat; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins; C000631270:Srcin1 protein, rat; D050257:Tubulin Modulators; D015739:Nocodazole