@article {69579, title = {Plasticity-induced actin polymerization in the dendritic shaft regulates intracellular AMPA receptor trafficking.}, journal = {Elife}, volume = {13}, year = {2024}, month = {2024 Aug 15}, abstract = {

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.

}, keywords = {Actins, Animals, Cells, Cultured, Dendrites, Exocytosis, Hippocampus, Neuronal Plasticity, Neurons, Polymerization, Protein Transport, Rats, Receptors, AMPA}, issn = {2050-084X}, doi = {10.7554/eLife.80622}, url = {https://doi.org/10.7554/eLife.80622}, author = {Wong, Victor C and Houlihan, Patrick R and Liu, Hui and Walpita, Deepika and DeSantis, Michael C and Liu, Zhe and O{\textquoteright}Shea, Erin K} } @article {64547, title = {Looking back and looking forward at Janelia.}, journal = {eLife}, volume = {8}, year = {2019}, month = {2019 Feb07}, pages = {e44826}, abstract = {

Starting a new research campus is a leap of faith. Only later, in the full measure of time, is it possible to take stock of what has worked and what could have been done better or differently. The Janelia Research Campus opened its doors 12 years ago. What has it achieved? What has it taught us? And where does Janelia go from here?

}, doi = {10.7554/eLife.44826}, author = {Rubin, Gerald M and O{\textquoteright}Shea, Erin K} } @article {49222, title = {Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing-bisphosphonates.}, journal = {eLife}, volume = {7}, year = {2018}, month = {2018 May 10}, abstract = {

Nitrogen-containing-bisphosphonates (N-BPs) are a class of drugs widely prescribed to treat osteoporosis and other bone-related diseases. Although previous studies have established that N-BPs function by inhibiting the mevalonate pathway in osteoclasts, the mechanism by which N-BPs enter the cytosol from the extracellular space to reach their molecular target is not understood. Here we implemented a CRISPRi-mediated genome-wide screen and identified (solute carrier family 37 member A3) as a gene required for the action of N-BPs in mammalian cells. We observed that SLC37A3 forms a complex with ATRAID (all-trans retinoic acid-induced differentiation factor), a previously identified genetic target of N-BPs. SLC37A3 and ATRAID localize to lysosomes and are required for releasing N-BP molecules that have trafficked to lysosomes through fluid-phase endocytosis into the cytosol. Our results elucidate the route by which N-BPs are delivered to their molecular target, addressing a key aspect of the mechanism of action of N-BPs that may have significant clinical relevance.

}, issn = {2050-084X}, doi = {10.7554/eLife.36620}, author = {Yu, Zhou and Surface, Lauren E and Park, Chong Yon and Horlbeck, Max A and Wyant, Gregory A and Abu-Remaileh, Monther and Peterson, Timothy R and Sabatini, David M and Weissman, Jonathan S and O{\textquoteright}Shea, Erin K} }