Nectin‐2α is localized at cholinergic neuron dendrites and regulates synapse formation in the medial habenula. Issue 2 (28th June 2020)

• Record Type: Journal Article
• Authors: Shiotani, Hajime; Miyata, Muneaki; Kameyama, Takeshi; Mandai, Kenji; Yamasaki, Miwako; Watanabe, Masahiko; Mizutani, Kiyohito; Takai, Yoshimi
• Is Part Of: Journal of comparative neurology. Volume 529:Issue 2(2021)
• Page Start: 450
• Page End: 477
• Publication Date: 2020-06-28
• Subjects: afadin -- cadherin -- cell adhesion -- cholinergic neuron -- medial habenula -- nectin -- synapse; Comparative neurobiology -- Periodicals; Neurology -- Periodicals; 616
• DOI: 10.1002/cne.24958
• Languages: English
• ISSNs: 0021-9967

Abstract

Abstract: The medial habenula (MHb) receives afferents from the triangular septum and the medial septal complex, projects efferents to the interpeduncular nucleus (IPN) in the midbrain to regulate dopamine and serotonin levels, and is implicated in stress, depression, memory, and nicotine withdrawal syndrome. We previously showed that the cell adhesion molecule nectin‐2α is localized at the boundary between adjacent somata of clustered cholinergic neurons and regulates the voltage‐gated A‐type K + channel Kv4.2 localization at membrane specializations in the MHb. This adhesion apparatus, named nectin‐2α spots, is not associated with the nectin‐binding protein afadin or any classic cadherins and their binding proteins p120‐catenin and β‐catenin. We showed here that nectin‐2α was additionally localized at cholinergic neuron dendrites in synaptic regions of the MHb. The genetic ablation of nectin‐2 reduced the number of synapses in the MHb without affecting their morphology. Nectin‐2α was associated with afadin, cadherin‐8, p120‐catenin, β‐catenin, and αN‐catenin, forming puncta adherentia junctions (PAJs). Nectin‐2α was observed in the IPN, but not in the triangular septum or the medial septal complex. The genetic ablation of nectin‐2 did not affect synapse formation in the IPN. These results indicate that nectin‐2α forms two types of adhesion apparatus in the MHb, namely nectin‐2α spots at neighboring somata and PAJs at neighboring dendrites, and that dendritic PAJs regulate synapse formation in the MHb. Abstract : Nectin‐2α, prominently expressed in the medial habenula (MHb), was localized at cholinergic neuron dendrites in synaptic regions of the MHb (clustered filled dots) in addition to the boundary between the adjacent somata of the clustered cholinergic neurons (edges of clustered open hexagons). This dendritic nectin‐2α formed puncta adherentia junctions cooperatively with afadin, cadherin‐8, p120‐catenin, β‐catenin, and αN‐catenin and regulated synapse formation.