Interaction between Teneurin-2 and microtubules via EB proteins provides a platform for GABAA receptor exocytosis

Elife. 2023 Jun 5:12:e83276. doi: 10.7554/eLife.83276.

Abstract

Neurons form dense neural circuits by connecting to each other via synapses and exchange information through synaptic receptors to sustain brain activities. Excitatory postsynapses form and mature on spines composed predominantly of actin, while inhibitory synapses are formed directly on the shafts of dendrites where both actin and microtubules (MTs) are present. Thus, it is the accumulation of specific proteins that characterizes inhibitory synapses. In this study, we explored the mechanisms that enable efficient protein accumulation at inhibitory postsynapse. We found that some inhibitory synapses function to recruit the plus end of MTs. One of the synaptic organizers, Teneurin-2 (TEN2), tends to localize to such MT-rich synapses and recruits MTs to inhibitory postsynapses via interaction with MT plus-end tracking proteins EBs. This recruitment mechanism provides a platform for the exocytosis of GABAA receptors. These regulatory mechanisms could lead to a better understanding of the pathogenesis of disorders such as schizophrenia and autism, which are caused by excitatory/inhibitory (E/I) imbalances during synaptogenesis.

Keywords: adhesion molecule; cell biology; microtubules; mouse; neuroscience; synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins* / metabolism
  • Exocytosis
  • Microtubules / metabolism
  • Neurons / metabolism
  • Receptors, GABA-A* / metabolism
  • Synapses / metabolism

Substances

  • Receptors, GABA-A
  • Actins

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.