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

Shi-Yan Sun; Lingyun Nie; Jing Zhang; Xue Fang; Hongmei Luo; Chuanhai Fu; Zhiyi Wei; Ai-Hui Tang

doi:10.4103/1673-5374.391301

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

Neural Regen Res. 2025 Jan 1;20(1):209-223. doi: 10.4103/1673-5374.391301. Epub 2023 Dec 21.

Authors

Shi-Yan Sun^{1

2}, Lingyun Nie^{1

3}, Jing Zhang^{4

5}, Xue Fang¹, Hongmei Luo^{1

2}, Chuanhai Fu^{1

3}, Zhiyi Wei^{4

5}, Ai-Hui Tang^{1

2}

Affiliations

¹ Hefei National Research Center for Physical Sciences at the Microscale, CAS Key Laboratory of Brain Function and Disease, Ministry of Education Key Laboratory for Membrane-less Organelles and Cellular Dynamics, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, China.
² Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei, Anhui Province, China.
³ CAS Center for Excellence in Molecular Cell Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, China.
⁴ Department of Neurobiology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong Province, China.
⁵ Brain Research Center, Southern University of Science and Technology, Shenzhen, Guangdong Province, China.

PMID: 38767486
DOI: 10.4103/1673-5374.391301

Abstract

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.