| Autor: |
Osamu, Nozawa, Muneaki, Miyata, Hajime, Shiotani, Takeshi, Kameyama, Ryouhei, Komaki, Tatsuhiro, Shimizu, Toshihiko, Kuriu, Yutaro, Kashiwagi, Yuka, Sato, Michinori, Koebisu, Atsu, Aiba, Shigeo, Okabe, Kiyohito, Mizutani, Yoshimi, Takai |
| Rok vydání: |
2022 |
| Zdroj: |
Development (Cambridge, England). |
| ISSN: |
1477-9129 |
| Popis: |
Ramified, polarized protoplasmic astrocytes interact with synapses via perisynaptic astrocyte processes (PAPs) to form tripartite synapses. These astrocyte-synapse interactions mutually regulate their structures and functions. However, molecular mechanisms for tripartite synapse formation remain elusive. We developed an in vitro co-culture system for mouse astrocytes and neurons that induced astrocyte ramifications and PAP formation. Co-cultured neurons were required for astrocyte ramifications in a neuronal activity-dependent manner and synaptically released glutamate and activation of astrocytic mGluR5 metabotropic glutamate receptor were likely involved in astrocyte ramifications. Astrocytic Necl-2/CADM1 trans-interacted with axonal Necl-3/CADM2, inducing astrocyte-synapse interactions and astrocyte functional polarization by recruiting EAAT1/2 glutamate transporters and Kir4.1 K+ channel to the PAPs, without affecting astrocyte ramifications. This Necl-2/3 trans-interaction increased functional synapse number. Thus, astrocytic Necl-2, synaptically released glutamate, and axonal Necl-3 cooperatively formed tripartite glutamatergic synapses in vitro. Studies on hippocampal mossy fiber synapses in Necl-3 knockout and Necl-2/3 double knockout mice confirmed these novel mechanisms for astrocyte-synapse interactions and astrocyte functional polarization in vivo. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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