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Presynaptic Rac1 in the hippocampus selectively regulates working memory.

Publication ,  Journal Article
Kim, J; Bustamante, E; Sotonyi, P; Maxwell, N; Parameswaran, P; Kent, JK; Wetsel, WC; Soderblom, EJ; Rácz, B; Soderling, SH
Published in: Elife
July 24, 2024

One of the most extensively studied members of the Ras superfamily of small GTPases, Rac1 is an intracellular signal transducer that remodels actin and phosphorylation signaling networks. Previous studies have shown that Rac1-mediated signaling is associated with hippocampal-dependent working memory and longer-term forms of learning and memory and that Rac1 can modulate forms of both pre- and postsynaptic plasticity. How these different cognitive functions and forms of plasticity mediated by Rac1 are linked, however, is unclear. Here, we show that spatial working memory in mice is selectively impaired following the expression of a genetically encoded Rac1 inhibitor at presynaptic terminals, while longer-term cognitive processes are affected by Rac1 inhibition at postsynaptic sites. To investigate the regulatory mechanisms of this presynaptic process, we leveraged new advances in mass spectrometry to identify the proteomic and post-translational landscape of presynaptic Rac1 signaling. We identified serine/threonine kinases and phosphorylated cytoskeletal signaling and synaptic vesicle proteins enriched with active Rac1. The phosphorylated sites in these proteins are at positions likely to have regulatory effects on synaptic vesicles. Consistent with this, we also report changes in the distribution and morphology of synaptic vesicles and in postsynaptic ultrastructure following presynaptic Rac1 inhibition. Overall, this study reveals a previously unrecognized presynaptic role of Rac1 signaling in cognitive processes and provides insights into its potential regulatory mechanisms.

Duke Scholars

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

July 24, 2024

Volume

13

Location

England

Related Subject Headings

  • rac1 GTP-Binding Protein
  • Signal Transduction
  • Presynaptic Terminals
  • Phosphorylation
  • Neuropeptides
  • Neuronal Plasticity
  • Mice, Inbred C57BL
  • Mice
  • Memory, Short-Term
  • Male
 

Citation

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MLA
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Kim, J., Bustamante, E., Sotonyi, P., Maxwell, N., Parameswaran, P., Kent, J. K., … Soderling, S. H. (2024). Presynaptic Rac1 in the hippocampus selectively regulates working memory. Elife, 13. https://doi.org/10.7554/eLife.97289
Kim, Jaebin, Edwin Bustamante, Peter Sotonyi, Nicholas Maxwell, Pooja Parameswaran, Julie K. Kent, William C. Wetsel, Erik J. Soderblom, Bence Rácz, and Scott H. Soderling. “Presynaptic Rac1 in the hippocampus selectively regulates working memory.Elife 13 (July 24, 2024). https://doi.org/10.7554/eLife.97289.
Kim J, Bustamante E, Sotonyi P, Maxwell N, Parameswaran P, Kent JK, et al. Presynaptic Rac1 in the hippocampus selectively regulates working memory. Elife. 2024 Jul 24;13.
Kim, Jaebin, et al. “Presynaptic Rac1 in the hippocampus selectively regulates working memory.Elife, vol. 13, July 2024. Pubmed, doi:10.7554/eLife.97289.
Kim J, Bustamante E, Sotonyi P, Maxwell N, Parameswaran P, Kent JK, Wetsel WC, Soderblom EJ, Rácz B, Soderling SH. Presynaptic Rac1 in the hippocampus selectively regulates working memory. Elife. 2024 Jul 24;13.

Published In

Elife

DOI

EISSN

2050-084X

Publication Date

July 24, 2024

Volume

13

Location

England

Related Subject Headings

  • rac1 GTP-Binding Protein
  • Signal Transduction
  • Presynaptic Terminals
  • Phosphorylation
  • Neuropeptides
  • Neuronal Plasticity
  • Mice, Inbred C57BL
  • Mice
  • Memory, Short-Term
  • Male