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Publication : Localization of nectin-2α at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage-gated A-type K<sup>+</sup> channel Kv4.2 in the medial habenula.

First Author  Shiotani H Year  2018
Journal  J Comp Neurol Volume  526
Issue  9 Pages  1527-1549
PubMed ID  29524214 Mgi Jnum  J:264046
Mgi Id  MGI:6192435 Doi  10.1002/cne.24425
Citation  Shiotani H, et al. (2018) Localization of nectin-2alpha at the boundary between the adjacent somata of the clustered cholinergic neurons and its regulatory role in the subcellular localization of the voltage-gated A-type K(+) channel Kv4.2 in the medial habenula. J Comp Neurol 526(9):1527-1549
abstractText  The medial habenula (MHb), implicated in stress, depression, memory, and nicotine withdrawal syndromes, receives septal inputs and sends efferents to the interpeduncular nucleus. We previously showed that the immunoglobulin-like cell adhesion molecules (CAMs) nectin-2alpha and nectin-2delta are expressed in astrocytes in the brain, but their expression in neurons remains unknown. We showed here by immunofluorescence microscopy that nectin-2alpha, but not nectin-2delta, was prominently expressed in the cholinergic neurons in the developing and adult MHbs and localized at the boundary between the adjacent somata of the clustered cholinergic neurons where the voltage-gated A-type K(+) channel Kv4.2 was localized. Analysis by immunoelectron microscopy on this boundary revealed that Kv4.2 was localized at the membrane specializations (MSs) with plasma membrane darkening in an asymmetrical manner, whereas nectin-2alpha was localized on the apposed plasma membranes mostly at the outside of these MSs, but occasionally localized at their edges and insides. Nectin-2alpha at this boundary was not colocalized with the nectin-2alpha-binding protein afadin, other CAMs, or their interacting peripheral membrane proteins, suggesting that nectin-2alpha forms a cell adhesion apparatus different from the Kv4.2-associated MSs. Genetic ablation of nectin-2 delayed the localization of Kv4.2 at the boundary between the adjacent somata of the clustered cholinergic neurons in the developing MHb. These results revealed the unique localization of nectin-2alpha and its regulatory role in the localization of Kv4.2 at the MSs in the MHb.
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