The interaction between KIF21A and KANK1 regulates dendritic morphology and synapse plasticity in neurons

Morphological alterations in dendritic spines have been linked to changes in functional communication between neurons that affect learning and memory.Kinesin-4 KIF21A helps organize the microtubule-actin network at the cell cortex by interacting with KANK1;however,whether KIF21A modulates dendritic structure and function in neurons remains unknown.In this study,we found that KIF21A was distributed in a subset of dendritic spines,and that these KIF21A-positive spines were larger and more structurally plastic than KIF21A-negative spines.Furthermore,the interaction between KIF21A and KANK1 was found to be critical for dendritic spine morphogenesis and synaptic plasticity.Knockdown of either KIF21A or KANK1 inhibited dendritic spine morphogenesis and dendritic branching,and these deficits were fully rescued by coexpressing full-length KIF21A or KANK1,but not by proteins with mutations disrupting direct binding between KIF21A and KANK1 or binding between KANK1 and talin1.Knocking down KIF21A in the hippocampus of rats inhibited the amplitudes of long-term potentiation induced by high-frequency stimulation and negatively impacted the animals’cognitive abilities.Taken together,our findings demonstrate the function of KIF21A in modulating spine morphology and provide insight into its role in synaptic function.

Tooth agenesis and craniofacial morphology in preorthodontic children with and without morphological deviations in the upper cervical spine

AIM: To analyze differences in prevalence and pattern of tooth agenesis and craniofacial morphology between non syndromic children with tooth agenesis with and without upper cervical spine morphological deviations and to analyze associations between craniofacial morphology and tooth agenesis in the two groups together. METHODS: One hundred and twenty-six pre-orthodontic children with tooth agenesis were divided into two groups with(19 children, mean age 11.9) and without(107 children, mean age 11.4) upper spine morphological deviations. Visual assessment of upper spine morphology and measurements of craniofacial morphology were performed on lateral cephalograms. Tooth agenesis was evaluated from orthopantomograms.RESULTS: No significant differences in tooth agenesis and craniofacial morphology were found between children with and without upper spine morphological deviations(2.2 ± 1.6 vs 1.94 ± 1.2, P > 0.05) but a tendency to a different tooth agenesis pattern were seen in children with morphological deviations in the upper spine. In the total group tooth agenesis was associated with the cranial base angle(n-s-ba, r = 0.23,P < 0.01), jaw angle(ML/RLar, r = 0.19, P < 0.05), mandibular inclination(NSL/ML, r =-0.21, P < 0.05), mandibular prognathia(s-n-pg, r = 0.25, P < 0.01), sagittal jaw relationship(ss-n-pg, r =-0.23, P < 0.5), overjet(r =-0.23, P < 0.05) and overbite(r =-0.25, P < 0.01). CONCLUSION: Etiology of tooth agenesis in children with upper spine morphological deviations was discussed. The results may be valuable for the early diagnosis and treatment planning of non syndromic children with tooth agenesis.

Initiation of dendritic NMDA spikes co-regulated via distance-dependent and dynamic distribution of the spine number and morphology in neuron dendrites

Dendritic spines are small membranous protrusions that receive synaptic inputs from other neurons,enabling the initiation of dendritic N-methyl-D-aspartic(NMDA)spikes and somatic action potentials.During learning and memory processes,both the number of spines on a dendrite and the morphology of individual spines are constantly changing.The individual influence of spine number and morphology on dendritic NMDA spikes has already been revealed,but the functional significance of the coregulation of spine number and morphology on NMDA spikes remains elusive.Here,we systematically investigated the initiation of local dendritic NMDA spikes by the dynamic distributions of the spine number and morphology on single dendrites in reconstructed neuron models.Different from the traditional cognition,we found the threshold number of spines required to generate local dendrite NMDA spikes on distal dendrites is fewer than that on proximal ones,because the thinner distal dendrites own higher impedance.As for the spine morphology,the presence of moreα-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid(AMPA)receptors on the spine leads to larger NMDA spikes rather than an increase in the spine dimension alone.Furthermore,we first suggested that a single dendrite containing spines with gradually increasing head diameters away from the soma could generate larger NMDA spikes than that irrational distribution of spine morphology containing spines with decreasing head diameters,which can be compensated by the increasing spine number.Complementarily,the distance-dependent distribution of spine number and morphology co-regulate the intension of dendritic NMDA spikes.These findings about the threshold for NMDA spikes provide novel insights into the role of the irrational dynamic distribution of the spine number and morphology in senescence and disease processes such as Alzheimer’s disease,schizophrenia,and Parkinson’s disease,which causes abnormal neuron firing.