Thrombospondin 1 accelerates synaptogenesis in hippocampal neurons through neuroligin 1

Nat Neurosci. 2010 Jan;13(1):22-4. doi: 10.1038/nn.2459. Epub 2009 Nov 15.

Abstract

In cultured rat hippocampal neurons, we found that thrombospondin 1 (TSP1) increased the speed of synapse formation in young neurons, but not the final density of synapses in mature neurons. TSP1 interacted with neuroligin 1 (NL1) and application of the NL1 extracellular domain blocked TSP1-induced synaptogenesis. Furthermore, knocking down endogenous NL1 inhibited TSP1's effect. Our results indicate that TSP1 accelerates the speed of synaptogenesis through NL1 in hippocampal neurons.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / genetics
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / metabolism
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / pharmacology
  • Cell Adhesion Molecules, Neuronal
  • Cells, Cultured
  • Disks Large Homolog 4 Protein
  • Embryo, Mammalian
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Green Fluorescent Proteins / genetics
  • Guanylate Kinases
  • Hippocampus / cytology*
  • Humans
  • Immunoprecipitation / methods
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Luminescent Proteins / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mutagenesis, Site-Directed / methods
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology*
  • Protein Binding
  • RNA, Small Interfering / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism
  • Synapses / drug effects*
  • Synapses / physiology
  • Synapsins / metabolism
  • Thrombospondin 1 / genetics
  • Thrombospondin 1 / pharmacology*
  • Transfection / methods

Substances

  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Adhesion Molecules, Neuronal
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Intracellular Signaling Peptides and Proteins
  • Luminescent Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • Receptors, LDL
  • SPZ1 protein, human
  • Synapsins
  • Thrombospondin 1
  • VLDL receptor
  • neuroligin 1
  • Green Fluorescent Proteins
  • Guanylate Kinases