Ras and Rap Signal Bidirectional Synaptic Plasticity via Distinct Subcellular Microdomains

Lei Zhang, Peng Zhang, Guangfu Wang, Huaye Zhang, Yajun Zhang, Yilin Yu, Mingxu Zhang, Jian Xiao, Piero Crespo, Johannes W Hell, Li Lin, Richard L. Huganir, J. Julius Zhu

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

How signaling molecules achieve signal diversity and specificity is a long-standing cell biology question. Here we report the development of a targeted delivery method that permits specific expression of homologous Ras-family small GTPases (i.e., Ras, Rap2, and Rap1) in different subcellular microdomains, including the endoplasmic reticulum, lipid rafts, bulk membrane, lysosomes, and Golgi complex, in rodent hippocampal CA1 neurons. The microdomain-targeted delivery, combined with multicolor fluorescence protein tagging and high-resolution dual-quintuple simultaneous patch-clamp recordings, allows systematic analysis of microdomain-specific signaling. The analysis shows that Ras signals long-term potentiation via endoplasmic reticulum PI3K and lipid raft ERK, whereas Rap2 and Rap1 signal depotentiation and long-term depression via bulk membrane JNK and lysosome p38MAPK, respectively. These results establish an effective subcellular microdomain-specific targeted delivery method and unveil subcellular microdomain-specific signaling as the mechanism for homologous Ras and Rap to achieve signal diversity and specificity to control multiple forms of synaptic plasticity. Zhang et al. develop an effective subcellular microdomain-specific targeted delivery method and demonstrate that homologous proteins (e.g., Ras and Rap) confine their signaling within distinct subcellular microdomains to achieve signal transduction diversity and specificity.

Original languageEnglish (US)
Pages (from-to)783-800.e4
JournalNeuron
Volume98
Issue number4
DOIs
StatePublished - May 16 2018

Fingerprint

Neuronal Plasticity
Lysosomes
Endoplasmic Reticulum
Long-Term Synaptic Depression
Lipids
ras Proteins
Membranes
Monomeric GTP-Binding Proteins
Long-Term Potentiation
Golgi Apparatus
Phosphatidylinositol 3-Kinases
Cell Biology
Rodentia
Signal Transduction
Fluorescence
Neurons
Proteins

Keywords

  • AMPA-R phorphorylation
  • AMPA-R trafficking
  • GluA1
  • GluA2
  • GluA2L
  • GluA4
  • nanocluster
  • organelle fractionation
  • subcellular signaling

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Zhang, L., Zhang, P., Wang, G., Zhang, H., Zhang, Y., Yu, Y., ... Zhu, J. J. (2018). Ras and Rap Signal Bidirectional Synaptic Plasticity via Distinct Subcellular Microdomains. Neuron, 98(4), 783-800.e4. https://doi.org/10.1016/j.neuron.2018.03.049

Ras and Rap Signal Bidirectional Synaptic Plasticity via Distinct Subcellular Microdomains. / Zhang, Lei; Zhang, Peng; Wang, Guangfu; Zhang, Huaye; Zhang, Yajun; Yu, Yilin; Zhang, Mingxu; Xiao, Jian; Crespo, Piero; Hell, Johannes W; Lin, Li; Huganir, Richard L.; Zhu, J. Julius.

In: Neuron, Vol. 98, No. 4, 16.05.2018, p. 783-800.e4.

Research output: Contribution to journalArticle

Zhang, L, Zhang, P, Wang, G, Zhang, H, Zhang, Y, Yu, Y, Zhang, M, Xiao, J, Crespo, P, Hell, JW, Lin, L, Huganir, RL & Zhu, JJ 2018, 'Ras and Rap Signal Bidirectional Synaptic Plasticity via Distinct Subcellular Microdomains', Neuron, vol. 98, no. 4, pp. 783-800.e4. https://doi.org/10.1016/j.neuron.2018.03.049
Zhang, Lei ; Zhang, Peng ; Wang, Guangfu ; Zhang, Huaye ; Zhang, Yajun ; Yu, Yilin ; Zhang, Mingxu ; Xiao, Jian ; Crespo, Piero ; Hell, Johannes W ; Lin, Li ; Huganir, Richard L. ; Zhu, J. Julius. / Ras and Rap Signal Bidirectional Synaptic Plasticity via Distinct Subcellular Microdomains. In: Neuron. 2018 ; Vol. 98, No. 4. pp. 783-800.e4.
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