Unusually rapid evolution of Neuroligin-4 in mice

Marc F. Bolliger, Jimin Pei, Stephan Maxeiner, Antony A. Boucard, Nick V. Grishin, Thomas C. Südhof

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Neuroligins (NLs) are postsynaptic cell-adhesion molecules that are implicated in humans in autism spectrum disorders because the genes encoding NL3 and NL4 are mutated in rare cases of familial autism. NLs are highly conserved evolutionarily, except that no NL4 was detected in the currently available mouse genome sequence assemblies. We now demonstrate that mice express a distant NL4 variant that rapidly evolved from other mammalian NL4 genes and that exhibits sequence variations even between different mouse strains. Despite its divergence, mouse NL4 binds neurexins and is transported into dendritic spines, suggesting that the core properties of NLs are retained in this divergent NL isoform. The selectively rapid evolution of NL4 in mice suggests that its function in the brain is under less stringent control than that of other NLs, shedding light on why its mutation in autism spectrum disorder patients is not lethal, but instead leads to a discrete developmental brain disorder.

Original languageEnglish (US)
Pages (from-to)6421-6426
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number17
DOIs
StatePublished - Apr 29 2008

Keywords

  • Autism
  • Cell-adhesion molecule
  • Neurexin synapse

ASJC Scopus subject areas

  • General

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