Neuroligin 1 regulates spines and synaptic plasticity via LIMK1/cofilin-mediated actin reorganization

J Cell Biol. 2016 Feb 15;212(4):449-63. doi: 10.1083/jcb.201509023.

Abstract

Neuroligin (NLG) 1 is important for synapse development and function, but the underlying mechanisms remain unclear. It is known that at least some aspects of NLG1 function are independent of the presynaptic neurexin, suggesting that the C-terminal domain (CTD) of NLG1 may be sufficient for synaptic regulation. In addition, NLG1 is subjected to activity-dependent proteolytic cleavage, generating a cytosolic CTD fragment, but the significance of this process remains unknown. In this study, we show that the CTD of NLG1 is sufficient to (a) enhance spine and synapse number, (b) modulate synaptic plasticity, and (c) exert these effects via its interaction with spine-associated Rap guanosine triphosphatase-activating protein and subsequent activation of LIM-domain protein kinase 1/cofilin-mediated actin reorganization. Our results provide a novel postsynaptic mechanism by which NLG1 regulates synapse development and function.

MeSH terms

  • Actin Cytoskeleton / enzymology*
  • Actin Depolymerizing Factors / metabolism*
  • Animals
  • Cell Adhesion Molecules, Neuronal / deficiency
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / enzymology*
  • Dendritic Spines / enzymology*
  • GTPase-Activating Proteins / metabolism
  • Genotype
  • HEK293 Cells
  • Hippocampus / cytology
  • Hippocampus / enzymology*
  • Humans
  • In Vitro Techniques
  • Lim Kinases / deficiency
  • Lim Kinases / genetics
  • Lim Kinases / metabolism*
  • Mice, Knockout
  • Neuronal Plasticity*
  • Phenotype
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • RNA Interference
  • Signal Transduction
  • Synapses / enzymology*
  • Time Factors
  • Transfection
  • rap1 GTP-Binding Proteins / metabolism

Substances

  • Actin Depolymerizing Factors
  • Cell Adhesion Molecules, Neuronal
  • GTPase-Activating Proteins
  • Sipa1l1 protein, mouse
  • neuroligin 1
  • Lim Kinases
  • Limk1 protein, mouse
  • Limk2 protein, mouse
  • rap1 GTP-Binding Proteins