AI Article Synopsis

  • Members of the Shank protein family (Shank1, Shank2, and Shank3) play crucial roles in forming the postsynaptic density at excitatory synapses by clustering receptors and connecting them to the actin cytoskeleton.
  • In this study, the researchers focused on the localization of Shank proteins at synapses in the hippocampus, specifically noting their presence at VGLUT1-positive synapses and mossy fiber contacts.
  • The study highlights that Shank proteins do not show costaining at VGLUT2-positive contacts, suggesting distinct molecular configurations between these synapses and indicating how SHANK mutations may impact specific glutamatergic networks related to neuropsychiatric disorders.

Article Abstract

Members of the Shank family of multidomain proteins (Shank1, Shank2, and Shank3) are core components of the postsynaptic density (PSD) of excitatory synapses. At synaptic sites Shanks serve as scaffolding molecules that cluster neurotransmitter receptors as well as cell adhesion molecules attaching them to the actin cytoskeleton. In this study we investigated the synapse specific localization of Shank1-3 and focused on well-defined synaptic contacts within the hippocampal formation. We found that all three family members are present only at VGLUT1-positive synapses, which is particularly visible at mossy fiber contacts. No costaining was found at VGLUT2-positive contacts indicating that the molecular organization of VGLUT2-associated PSDs diverges from classical VGLUT1-positive excitatory contacts in the hippocampus. In light of SHANK mutations in neuropsychiatric disorders, this study indicates which glutamatergic networks within the hippocampus will be primarily affected by shankopathies.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4844616PMC
http://dx.doi.org/10.3389/fncel.2016.00106DOI Listing

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