Molecular basis of interactions between CaMKII and α-actinin-2 that underlie dendritic spine enlargement

Curtis, Ashton J; Zhu, Jian; Penny, Christopher J; Gold, Matthew G

doi:10.7554/elife.85008

Cited by 3 publications

(1 citation statement)

References 72 publications

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“…This protein can anchor and organize other proteins in the dendritic spine, such as CaMKII ( Robison et al, 2005 ), the receptor NMDAR ( Wyszynski et al, 1997 ), and certain channel proteins that allow calcium ions to enter cells ( Hall et al, 2013 ). Now, in eLife, Matthew Gold from University College London and colleagues – including Ashton Curtis and Jian Zhu as joint first authors – report new insights into the molecular interactions between CaMKII, alpha-actinin-2, and a subunit of NMDAR called GluN2B ( Curtis et al, 2023 ; Figure 1 ).…”

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confidence: 99%

Changing the size of dendritic spines

Saneyoshi

2023

eLife

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confidence: 99%

Changing the size of dendritic spines

Saneyoshi

2023

eLife

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Disruption of autism-associatedPcdh9gene leads to transcriptional alterations, synapses overgrowth and aberrant excitatory transmission in the CA1

Miozzo,

Murru,

Maiellano

et al. 2024

Preprint

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Protocadherins are cell adhesion molecules with crucial role in cell-cell contacts, whose mutations or altered expression have been implicated in multiple brain disorders. In particular, growing evidence links genetic alterations in Protocadherin 9 (PCDH9) gene with Autism Spectrum Disorder (ASD) and Major Depression Disorder (MDD). Furthermore, Pcdh9 deletion induces neuronal defects in the mouse somatosensory cortex, accompanied by sensorimotor and memory impairment. However, the synaptic and molecular mechanisms underlying Pcdh9 physiological function and its involvement in brain pathology remain largely unknown. To this aim, we conducted a comprehensive investigation of PCDH9 role in the mouse hippocampus at the ultrastructural, biochemical, transcriptomic, electrophysiological and network level. We show that PCDH9 mainly localizes at glutamatergic synapses and its expression peaks in the first week after birth, a crucial time window for synaptogenesis. Strikingly, Pcdh9 KO neurons exhibit oversized presynaptic terminal and postsynaptic density (PSD) in the CA1. Synapse overgrowth is sustained by the broad up-regulation of synaptic genes and the dysregulation of key drivers of synapse morphogenesis, as revealed by single-nucleus RNAseq. Synaptic and transcriptional defects are accompanied by increased EPSC frequency and disturbances in the hippocampal network activity of Pcdh9 KO mice. In conclusion, our work indicates that Pcdh9 regulates the morphology and function of excitatory synapses in the CA1, thereby affecting glutamatergic transmission in hippocampal circuitries.

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Expression of synaptic proteins and development of dendritic spines in fetal and postnatal neocortex of the pig, the European wild boar Sus scrofa

Sobierajski,

Czubay,

Schmidt

et al. 2024

Preprint

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Synapse formation is a critical step in neuronal development. Current knowledge is largely based on altricial rodents where synapse formation and maturation proceed largely postnatally. In precocially born mammals such as guinea pig presynapse and spine formation start well before birth. Here, we analysed the developmental expression of proteins associated with synapse formation and maturation together with the development of basal dendritic spines of pyramidal neurons of visual and somatosensory cortex of the pig, an emerging translational model for human neurodegenerative disorders. A total of 23 selected proteins was quantified with Western blots. Most were detectable from midgestation embryonal day (E) 65 onwards. About half reached the adult expression level seen in postnatal day (P) 90 pig cortex already two weeks before birth (gestation 114 days) in somatosensory, albeit not yet in visual cortex. For instance, major molecular components of synaptic plasticity such as GluN2B, CamKIIα, α-actinin-2, synaptopodin and T286 phosphorylated CamKIIα were expressed at E100 in somatosensory cortex. Dendritic spine type quantification with DiI-labeled material revealed an increase of total dendritic protrusion from E70 onwards. The increase was steepest in somatosensory cortex which had, at E110, a proportion of mushroom spines equal to the proportion present at P90. Together, matching the ungulate life history, a rapid development of functional synaptic connectivity in prenatal somatosensory cortex serves the somatomotor abilities essentially required by the newborn nest-fledgling. Results support the “cascading” model of a sequential maturation of cortical areas, and in precocial species the cascade starts well before birth.

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Molecular basis of interactions between CaMKII and α-actinin-2 that underlie dendritic spine enlargement

Cited by 3 publications

References 72 publications

Changing the size of dendritic spines

Changing the size of dendritic spines

Disruption of autism-associatedPcdh9gene leads to transcriptional alterations, synapses overgrowth and aberrant excitatory transmission in the CA1

Expression of synaptic proteins and development of dendritic spines in fetal and postnatal neocortex of the pig, the European wild boar Sus scrofa

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