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Published on: March 30, 2018
Kif15 orchestrates neuronal-microglial communication via CX3CL1 to impede nerve regeneration
Ronghua Wu1, Wei Zhang1, Xiaowei Qian1
1Jiangsu Key Laboratory of Tissue Engineering and Neuroregeneration, Key Laboratory of Neuroregeneration of Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
Abstract:
Kinesins, a class of microtubule (MT)-dependent molecular motors, regulate MT dynamics and MT-mediated transport. We previously identified Kif15 (kinesin-12) as a key player in axonal growth by modulating MT remodeling during neuronal development, and more recently, its involvement in protein localization. In this study, we observed that Kif15 knockout (Kif15 KO) mice exhibited accelerated functional recovery after sciatic nerve injury. To investigate the cellular responses underlying this enhanced recovery after axotomy, spinal cord tissues from the injured regions were collected for single-nucleus RNA sequencing (snRNA-seq). The snRNA-seq results revealed differential genes expression in neurons, indicating a neuroprotective shift in Kif15 KO mice, and in microglia, where a repair-promoting and synapse-modulating profile was observed. Notably, the CX3CL1-CX3CR1 signaling pathway, critical for neuronal-microglial communication, was downregulated in Kif15 KO mice compared to wild-type controls. Further molecular analysis indicated that Kif15 facilitated the expression and localization of neuronal CX3CL1, which, in turn, influenced microglial function via the receptor CX3CR1. Our findings highlight a novel role for Kif15 in regulating neuronal-microglial communication through modulation of CX3CL1 signaling.
Insights
Kinesin-15 (Kif15) deficiency accelerates nerve injury recovery by altering neuronal-microglial communication. Kif15 regulates CX3CL1 signaling, impacting neuroprotection and repair after sciatic nerve injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Kinesins are microtubule-dependent motors regulating cellular processes.
- Kinesin-15 (Kif15) is involved in axonal growth and protein localization.
- Kif15's role in nerve injury response was previously unknown.
Purpose of the Study:
- To investigate the role of Kif15 in functional recovery after sciatic nerve injury.
- To elucidate the cellular mechanisms underlying enhanced recovery in Kif15 knockout mice.
- To explore Kif15's influence on neuronal-microglial communication.
Main Methods:
- Sciatic nerve injury model in Kif15 knockout and wild-type mice.
- Single-nucleus RNA sequencing (snRNA-seq) of spinal cord tissues.
- Molecular analysis of CX3CL1-CX3CR1 signaling pathway.
Main Results:
- Kif15 knockout mice showed accelerated functional recovery post-injury.
- snRNA-seq revealed neuroprotective gene expression in neurons and repair-promoting profiles in microglia.
- Downregulation of CX3CL1-CX3CR1 signaling was observed in Kif15 knockout mice.
- Kif15 was found to facilitate neuronal CX3CL1 expression and localization.
Conclusions:
- Kif15 plays a novel role in modulating neuronal-microglial communication.
- Kif15 regulates nerve injury recovery via the CX3CL1 signaling pathway.
- Targeting Kif15 may offer therapeutic strategies for nerve regeneration.
