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

JOURNAL/nrgr/04.03/01300535-202501000-00029/figure1/v/2024-05-14T021156Z/r/image-tiff 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.

Correlative Assembly of Subsynaptic Nanoscale Organizations During Development.

Nanoscale organization of presynaptic proteins determines the sites of transmitter release, and its alignment with assemblies of postsynaptic receptors through nanocolumns is suggested to optimize the efficiency of synaptic transmission. However, it remains unknown how these nano-organizations are formed during development. In this study, we used super-resolution stochastic optical reconstruction microscopy (STORM) imaging technique to systematically analyze the evolvement of subsynaptic organization of three key synaptic proteins, namely, RIM1/2, GluA1, and PSD-95, during synapse maturation in cultured hippocampal neurons. We found that volumes of synaptic clusters and their subsynaptic heterogeneity increase as synapses get matured. Synapse sizes of presynaptic and postsynaptic compartments correlated well at all stages, while only more mature synapses demonstrated a significant correlation between presynaptic and postsynaptic nano-organizations. After a long incubation with an inhibitor of action potentials or AMPA receptors, both presynaptic and postsynaptic compartments showed increased synaptic cluster volume and subsynaptic heterogeneity; however, the trans-synaptic alignment was intact. Together, our results characterize the evolvement of subsynaptic protein architectures during development and demonstrate that the nanocolumn is organized more likely by an intrinsic mechanism and independent of synaptic activities.