The X-linked intellectual disability protein IL1RAPL1 regulates dendrite complexity

Caterina Montani, Mariana Ramos-Brossier, Luisa Ponzoni, Laura Gritti, Andrzej W. Cwetsch, Daniela Braida, Yoann Saillour, Benedetta Terragni, Massimo Mantegazza, Mariaelvina Sala, Chiara Verpelli, Pierre Billuart, Carlo Sala

Research output: Contribution to journalArticle

Abstract

Mutations and deletions of the interleukin-1 receptor accessory protein like 1 (IL1RAPL1) gene, located on the X chromosome, are associated with intellectual disability (ID) and autism spectrum disorder (ASD). IL1RAPL1 protein is located at the postsynaptic compartment of excitatory synapses and plays a role in synapse formation and stabilization. Here, using primary neuronal cultures and Il1rapl1-KO mice, we characterized the role of IL1RAPL1 in regulating dendrite morphology. In Il1rapl1-KO mice we identified an increased number of dendrite branching points in CA1 and CA2 hippocampal neurons associated to hippocampal cognitive impairment. Similarly, induced pluripotent stem cell-derived neurons from a patient carrying a null mutation of the IL1RAPL1 gene had more dendrites. In hippocampal neurons, the overexpression of full-length IL1RAPL1 and mutants lacking part of C-terminal domains leads to simplified neuronal arborization. This effect is abolished when we overexpressed mutants lacking part of N-terminal domains, indicating that the IL1RAPL1 extracellular domain is required for regulating dendrite development. We also demonstrate that PTPδ interaction is not required for this activity, while IL1RAPL1 mediates the activity of IL-1β on dendrite morphology. Our data reveal a novel specific function for IL1RAPL1 in regulating dendrite morphology that can help clarify how changes in IL1RAPL1-regulated pathways can lead to cognitive disorders in humans.

Original languageEnglish
Pages (from-to)6606-6627
Number of pages22
JournalJournal of Neuroscience
Volume37
Issue number28
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Interleukin-1 Receptor Accessory Protein
Dendrites
Intellectual Disability
Proteins
Neurons
Synapses
Induced Pluripotent Stem Cells
Neuronal Plasticity
Sequence Deletion
X Chromosome
Interleukin-1
Genes

Keywords

  • Dendrites
  • Hippocampus
  • Human iPS cells
  • IL1-β
  • Synapses
  • X-linked ID

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Montani, C., Ramos-Brossier, M., Ponzoni, L., Gritti, L., Cwetsch, A. W., Braida, D., ... Sala, C. (2017). The X-linked intellectual disability protein IL1RAPL1 regulates dendrite complexity. Journal of Neuroscience, 37(28), 6606-6627. https://doi.org/10.1523/JNEUROSCI.3775-16.2017

The X-linked intellectual disability protein IL1RAPL1 regulates dendrite complexity. / Montani, Caterina; Ramos-Brossier, Mariana; Ponzoni, Luisa; Gritti, Laura; Cwetsch, Andrzej W.; Braida, Daniela; Saillour, Yoann; Terragni, Benedetta; Mantegazza, Massimo; Sala, Mariaelvina; Verpelli, Chiara; Billuart, Pierre; Sala, Carlo.

In: Journal of Neuroscience, Vol. 37, No. 28, 01.01.2017, p. 6606-6627.

Research output: Contribution to journalArticle

Montani, C, Ramos-Brossier, M, Ponzoni, L, Gritti, L, Cwetsch, AW, Braida, D, Saillour, Y, Terragni, B, Mantegazza, M, Sala, M, Verpelli, C, Billuart, P & Sala, C 2017, 'The X-linked intellectual disability protein IL1RAPL1 regulates dendrite complexity', Journal of Neuroscience, vol. 37, no. 28, pp. 6606-6627. https://doi.org/10.1523/JNEUROSCI.3775-16.2017
Montani C, Ramos-Brossier M, Ponzoni L, Gritti L, Cwetsch AW, Braida D et al. The X-linked intellectual disability protein IL1RAPL1 regulates dendrite complexity. Journal of Neuroscience. 2017 Jan 1;37(28):6606-6627. https://doi.org/10.1523/JNEUROSCI.3775-16.2017
Montani, Caterina ; Ramos-Brossier, Mariana ; Ponzoni, Luisa ; Gritti, Laura ; Cwetsch, Andrzej W. ; Braida, Daniela ; Saillour, Yoann ; Terragni, Benedetta ; Mantegazza, Massimo ; Sala, Mariaelvina ; Verpelli, Chiara ; Billuart, Pierre ; Sala, Carlo. / The X-linked intellectual disability protein IL1RAPL1 regulates dendrite complexity. In: Journal of Neuroscience. 2017 ; Vol. 37, No. 28. pp. 6606-6627.
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