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bioRxiv · 10.1101/2022.05.29.493906

Plasticity-induced actin polymerization in the dendritic shaft regulates intracellular AMPA receptor trafficking

Wong, V. C.·Houlihan, P. R.·Liu, H.·Walpita, D.·DeSantis, M. C.·Liu, Z.·O'Shea, E. K.
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Abstract

AMPA-type receptors (AMPARs) are rapidly inserted into synapses undergoing long-term potentiation (LTP) to increase synaptic transmission, but how AMPAR-containing vesicles are selectively trafficked to these synapses during LTP is not known. Here we developed a strategy to label AMPAR GluA1 subunits expressed from the endogenous loci of rat hippocampal neurons such that the motion of GluA1-containing vesicles in time-lapse sequences can be characterized using single-particle tracking and mathematical modeling. We find that GluA1- containing vesicles are confined and concentrated near sites of stimulation-induced plasticity. We show that confinement is mediated by actin polymerization, which hinders the active transport of GluA1-containing vesicles along the length of the dendritic shaft by modulating the rheological properties of the cytoplasm. Actin polymerization also facilitates myosin-mediated transport of GluA1-containing vesicles to exocytic sites. We conclude that neurons utilize F- actin to increase vesicular GluA1 reservoirs and promote exocytosis proximal to the sites of neuronal activity.

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Wong, V. C., Houlihan, P. R., Liu, H., Walpita, D., DeSantis, M. C., Liu, Z., O'Shea, E. K.. 2022-05-29. Plasticity-induced actin polymerization in the dendritic shaft regulates intracellular AMPA receptor trafficking. https://doi.org/10.1101/2022.05.29.493906

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