Plasticity-induced actin polymerization in the dendritic shaft regulates intracellular AMPA receptor trafficking.
AMPA-type receptors (AMPARs) are rapidly inserted into synapses undergoing plasticity to increase synaptic transmission, but it is not fully understood if and how AMPAR-containing vesicles are selectively trafficked to these synapses. Here, we developed a strategy to label AMPAR GluA1 subunits expressed from their endogenous loci in cultured rat hippocampal neurons and characterized the motion of GluA1-containing vesicles using single-particle tracking and mathematical modeling. We find that GluA1-containing vesicles are confined and concentrated near sites of stimulation-induced structural 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 synaptic activity.
Pubmed ID: 39146380 RIS Download
Research resources used in this publication
- PX552 (RRID:Addgene_60958) (plasmid)
- PX551 (RRID:Addgene_60957) (plasmid)
- pEGFP-MyosinVb-Ctail (RRID:Addgene_110170) (plasmid)
- pEGFP-MyosinVa-Ctail (RRID:Addgene_110169) (plasmid)
- pCMV2-SEP-GluA1 (M1) (RRID:Addgene_64942) (plasmid)
- pCMV-PfV-Sapphire-IRES-DSRed (RRID:Addgene_116934) (plasmid)
- pAS1NB c Rosella I (RRID:Addgene_71245) (plasmid)
- LZ10 PBREBAC-H2BHalo (RRID:Addgene_91564) (plasmid)
- ITPKA-mNeonGreen (RRID:Addgene_98883) (plasmid)
- pAAV.hSyn.eGFP.WPRE.bGH (RRID:Addgene_105539) (plasmid)
- pENN.AAV.CAG.tdTomato.WPRE.SV40 (RRID:Addgene_105554) (plasmid)
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