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

View ORCID ProfileV. C. Wong, P.R. Houlihan, H. Liu, D. Walpita, View ORCID ProfileM.C. DeSantis, View ORCID ProfileZ. Liu, View ORCID ProfileE. K. O’Shea
doi: https://doi.org/10.1101/2022.05.29.493906
V. C. Wong
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, 20147
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  • For correspondence: wongv@janelia.hhmi.org
P.R. Houlihan
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, 20147
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H. Liu
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, 20147
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D. Walpita
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, 20147
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M.C. DeSantis
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, 20147
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Z. Liu
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, 20147
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E. K. O’Shea
1Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, 20147
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  • ORCID record for E. K. O’Shea
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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.

Competing Interest Statement

Erin K OShea is the President of the Howard Hughes Medical Institute, one of the three founding funders of eLife.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted May 29, 2022.
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Plasticity-induced actin polymerization in the dendritic shaft regulates intracellular AMPA receptor trafficking
V. C. Wong, P.R. Houlihan, H. Liu, D. Walpita, M.C. DeSantis, Z. Liu, E. K. O’Shea
bioRxiv 2022.05.29.493906; doi: https://doi.org/10.1101/2022.05.29.493906
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Plasticity-induced actin polymerization in the dendritic shaft regulates intracellular AMPA receptor trafficking
V. C. Wong, P.R. Houlihan, H. Liu, D. Walpita, M.C. DeSantis, Z. Liu, E. K. O’Shea
bioRxiv 2022.05.29.493906; doi: https://doi.org/10.1101/2022.05.29.493906

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