Fig. 1: Increased CaMKIIα kinase activity and enlarged dendritic spine heads of hippocampal neurons in male CaMKIIα P212L Ht mice. | Translational Psychiatry

Fig. 1: Increased CaMKIIα kinase activity and enlarged dendritic spine heads of hippocampal neurons in male CaMKIIα P212L Ht mice.

From: A hyper-activatable CAMK2A variant associated with intellectual disability causes exaggerated long-term potentiation and learning impairments

Fig. 1

A Structure of single human CaMKIIα subunit (extracted from a holoenzyme structure: PDB: 3SOA) with the kinase domain (pink), regulatory domain (green), and association domain (straw yellow). Locations of Pro212 and Thr286-autophosphorylation sites are indicated. Multiple sequence alignment of aa193–218 in human CaMKIIα with the indicated animal species. Pro212 is highlighted in red. The alignment was carried out using UniProt. UniProt accession numbers: Human; Q9UQM7, Mouse; P11798, Chicken; A0A8V0YT86, Zebrafish; Q32PV2. B, C Effects of CaMKIIα P212L mutation on the autophosphorylation levels at T286 and expression levels of CaMKIIα protein. The synaptic fractions were prepared from whole brain homogenates and analyzed by Western blotting. Representative blots are shown in the left panels. (B) Male mice (WT: n = 10, Ht: n = 11), and (C) female mice (WT: n = 8, Ht: n = 8) (unpaired Student’s t-test). WT: wild-type; Ht: CaMKIIα P212L heterozygous mutant; M: male; F: female. D Intracranial injection of AAV-PHP.eB-CBh-Cre and AAV-PHP.eB-CBh-FLEx-EGFP into the cerebral lateral ventricles of neonatal mice to sparsely label pyramidal neurons of CA1 field of the hippocampus. E Representative images of secondary dendrites. The white arrowheads indicate mushroom-shaped dendritic spines. Mushroom spines are defined as spines with a head diameter larger than 0.4 μm. Scale bar, 2 μm. F, G Mushroom spine head diameters were measured from CaMKIIα P212L neurons versus WT neurons. Average (left panels, unpaired Student’s t-test) and cumulative distribution (right panels, Kolmogorov-Smirnov test) of spine diameter are affected in male CaMKIIα P212L mice. H Mushroom-type spine density was not affected in CaMKIIα P212L mice. Male: n = 27 spines from 6 WT mice, n = 25 spines from 5 Ht mice. Female: n = 15 spines from 3 WT mice, n = 14 spines from 3 Ht mice (unpaired Student’s t-test). Data represent mean ± SEM. *p < 0.05, ***p < 0.001.

Back to article page