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Publication : Nectin-2α is localized at cholinergic neuron dendrites and regulates synapse formation in the medial habenula.

First Author  Shiotani H Year  2021
Journal  J Comp Neurol Volume  529
Issue  2 Pages  450-477
PubMed ID  32452538 Mgi Jnum  J:305183
Mgi Id  MGI:6510299 Doi  10.1002/cne.24958
Citation  Shiotani H, et al. (2021) Nectin-2alpha is localized at cholinergic neuron dendrites and regulates synapse formation in the medial habenula. J Comp Neurol 529(2):450-477
abstractText  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-2alpha 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-2alpha spots, is not associated with the nectin-binding protein afadin or any classic cadherins and their binding proteins p120-catenin and beta-catenin. We showed here that nectin-2alpha 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-2alpha was associated with afadin, cadherin-8, p120-catenin, beta-catenin, and alphaN-catenin, forming puncta adherentia junctions (PAJs). Nectin-2alpha 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-2alpha forms two types of adhesion apparatus in the MHb, namely nectin-2alpha spots at neighboring somata and PAJs at neighboring dendrites, and that dendritic PAJs regulate synapse formation in the MHb.
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