NCAM2 Regulates Dendritic and Axonal Differentiation through the Cytoskeletal Proteins MAP2 and 14-3-3

Antoni Parcerisas, Lluís Pujadas, Alba Ortega-Gascó, Bartomeu Perelló-Amorós, Ricardo Viais, Keiko Hino, Joana Figueiro-Silva, Anna La Torre, Ramón Trullás, Sergi Simó, Jens Lüders, Eduardo Soriano

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Neural cell adhesion molecule 2 (NCAM2) is involved in the development and plasticity of the olfactory system. Genetic data have implicated the NCAM2 gene in neurodevelopmental disorders including Down syndrome and autism, although its role in cortical development is unknown. Here, we show that while overexpression of NCAM2 in hippocampal neurons leads to minor alterations, its downregulation severely compromises dendritic architecture, leading to an aberrant phenotype including shorter dendritic trees, retraction of dendrites, and emergence of numerous somatic neurites. Further, our data reveal alterations in the axonal tree and deficits in neuronal polarization. In vivo studies confirm the phenotype and reveal an unexpected role for NCAM2 in cortical migration. Proteomic and cell biology experiments show that NCAM2 molecules exert their functions through a protein complex with the cytoskeletal-associated proteins MAP2 and 14-3-3γ and ζ. We provide evidence that NCAM2 depletion results in destabilization of the microtubular network and reduced MAP2 signal. Our results demonstrate a role for NCAM2 in dendritic formation and maintenance, and in neural polarization and migration, through interaction of NCAM2 with microtubule-associated proteins.

Original languageEnglish (US)
Pages (from-to)3781-3799
Number of pages19
JournalCerebral cortex (New York, N.Y. : 1991)
Volume30
Issue number6
DOIs
StatePublished - May 18 2020

Keywords

  • 14-3-3
  • dendritogenesis
  • MAP2
  • microtubules
  • NCAM2
  • neuronal differentiation

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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