Abstract
CASK-interactive proteins, Caskin1 and Caskin2, are multidomain neuronal scaffold proteins. Recent data from Caskin1 knockout animals indicated only a mild role of Caskin1 in anxiety and pain perception. In this work, we show that deletion of both Caskins leads to severe deficits in novelty recognition and spatial memory. Ultrastructural analyses revealed a reduction in synaptic profiles and dendritic spine areas of CA1 hippocampal pyramidal neurons of double knockout mice. Loss of Caskin proteins impaired LTP induction in hippocampal slices, while miniature EPSCs in dissociated hippocampal cultures appeared to be unaffected. In cultured Caskin knockout hippocampal neurons, overexpressed Caskin1 was enriched in dendritic spine heads and increased the amount of mushroom-shaped dendritic spines. Chemically induced LTP (cLTP) mediated enlargement of spine heads was augmented in the knockout mice and was not influenced by Caskin1. Immunocytochemistry and immunoprecipitation confirmed that Shank2, a master scaffold of the postsynaptic density, and Caskin1 co-localized within the same complex. Phosphorylation of AMPA receptors was specifically altered by Caskin deficiency and was not elevated by cLTP treatment further. Taken together, our results prove a previously unnoticed postsynaptic role of Caskin scaffold proteins and indicate that Caskins influence learning abilities via regulating spine morphology and AMPA receptor localisation.
Highlights
CASK-interactive proteins, Caskin[1] and Caskin[2], are multidomain neuronal scaffold proteins
We prove that the lack of Caskins and the overexpression of Caskin[1] altered dendritic spine morphology of hippocampal neurons in an opposite manner
As post-Hz stimulus for sec (HFS) normalized distance values were increased compared to the pre-HFS values in both Caskin dHZ and Caskin dKO recordings, our results indicate that E/S facilitation was induced by HFS in both groups but the baseline and the post-HFS values were significantly lower in the Caskin dKO group (Fig. 3I)
Summary
CASK-interactive proteins, Caskin[1] and Caskin[2], are multidomain neuronal scaffold proteins. Our results prove a previously unnoticed postsynaptic role of Caskin scaffold proteins and indicate that Caskins influence learning abilities via regulating spine morphology and AMPA receptor localisation. Activity-dependent long-term synaptic plasticity in adult neural networks depends on the strengthening or weakening of existing synapses and formation of new contact sites These effects include structural changes due to altered cytoskeletal dynamics, shape or arborisation[1,2,3,4] or electrophysiological changes in intrinsic membrane properties depending on the type, quantity or localisation of ion channels and neurotransmitter receptors within the plasma membrane[5,6]. CASK-interactive proteins, Caskin[1] and Caskin[2], are multidomain neuronal scaffold proteins[13]. Caskin[1] has been proposed to play a role in synaptic functions via interacting with CASK protein near the presynaptic plasma membrane[13,17,23]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
