The SK2-long isoform directs synaptic localization and function of SK2-containing channels

Abstract

SK2-containing channels are expressed in the postsynaptic density (PSD) of dendritic spines on mouse CA1 pyramidal neurons, and influence synaptic responses, plasticity, and learning. The SK2 gene encodes two isoforms differing only in the length of the N-terminal domain. SK2-Long (SK2-L) and SK2-Short (SK2-S) are co-expressed in CA1 pyramidal neurons and likely form heteromeric channels. In mice lacking SK2-L (SK2-Sonly mice), SK2-S-containing channels were expressed in the extrasynaptic membrane, but were excluded from the PSD. The SK channel contribution to EPSPs was absent in SK2-Sonly mice, and was restored by SK2-L re-expression. In slices from wild type mice, blocking SK channels increased the amount of long-term potentiation (LTP) induced in area CA1 but was without effect in SK2-Sonly mice. Further, SK2-Sonly mice outperformed wild type mice in the novel object recognition task. These results show that SK2-L directs synaptic SK2-containing channel expression, important for normal synaptic signaling, plasticity, and learning.

Localization and Targeting of GIRK Channels in Mammalian Central Neurons

“…Although the SDS detergent denatures surface proteins by unfolding their secondary, tertiary, and quaternary structures, antigenicity is often retained (Fujimoto, 1995) in a similar way to when immunoblot with SDS-polyacrylamide gel electrophoresis is employed. The main advantages of SDS-FRL are its high sensitivity (the highest among all iEM techniques) and allowance for quantitative studies of different markers/antigens along the whole neuronal surface (Allen et al, 2011;García-Negredo et al, 2014;Indriati et al, 2013;Kasugai et al, 2010;Fig. 1D).…”

“…1D). The main disadvantage is that fracture surface replicas are performed randomly, and due to the scarcity of morphological clues, it is difficult to identify cell types and subcellular compartments without the use of double labeling with specific markers (Allen et al, 2011;Indriati et al, 2013;Kasugai et al, 2010;Tarusawa et al, 2009).…”

Targeting of Tumor Necrosis Factor Alpha Receptors as a Therapeutic Strategy for Neurodegenerative Disorders

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Activity-Dependent Genes in Mouse Olfactory Sensory Neurons

“…Eml5 proteins are found in either axons or secretory vesicles (Schäfer et al 2000;O'Connor et al 2004;Serizawa et al 2006;Uemura et al 2007;Takeyama et al 2009;Suckale and Solimena 2010;Allen et al 2011;Williams et al 2011). Kirrel2 and Kirrel3 are important for the fasciculation and targeting of OSN axons.…”