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Related Experiment Videos

Transsynaptic signaling by postsynaptic synapse-associated protein 97.

Maria Paz Regalado1, Ryan T Terry-Lorenzo, Clarissa L Waites

  • 1Department of Psychiatry and Behavioral Sciences, Nancy Pritzker Laboratory, Stanford University, Palo Alto, California 94304-5485, USA.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
|February 24, 2006
PubMed
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Postsynaptic expression of synapse-associated protein 97 (SAP97) drives presynaptic growth and function. This scaffolding protein coordinates synapse development and plasticity through transsynaptic signaling.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • The mechanisms linking postsynaptic changes to presynaptic structure and function remain largely unknown.
  • Synaptic scaffolding proteins play critical roles in organizing neuronal connections.

Purpose of the Study:

  • To investigate the presynaptic effects of postsynaptic expression of membrane-associated guanylate kinase family proteins.
  • To elucidate the role of synapse-associated protein 97 (SAP97) in coordinating synaptic structure and function.

Main Methods:

  • Examined presynaptic consequences of postsynaptic SAP97, PSD-95, and SAP102 expression.
  • Measured presynaptic protein content, active zone size, and FM4-64 dye uptake.
  • Investigated the molecular domains of SAP97 required for its effects and identified interacting postsynaptic proteins and transsynaptic signaling pathways.

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Main Results:

  • Postsynaptic SAP97 significantly increased presynaptic protein content and active zone size more than PSD-95 or SAP102.
  • SAP97 enhanced presynaptic function, indicated by increased FM4-64 uptake.
  • SAP97's structural effects depended on its PDZ, N-terminal, and guanylate kinase domains, recruiting proteins like glutamate receptor 1 and Shank1a.
  • Inhibiting cadherins, integrins, or EphB/ephrinB signaling reduced SAP97-induced presynaptic growth.

Conclusions:

  • Postsynaptic SAP97 plays a key role in coordinating synapse development and plasticity.
  • SAP97 recruits a postsynaptic protein complex that promotes presynaptic terminal growth and function.
  • Multiple transsynaptic molecular interactions mediate SAP97's effects on presynaptic structure and function.