한빛사논문
- 조회666
Jong-Heon Kim1, Hyun-Gug Jung2,3, Ajung Kim2, Hyun Soo Shim4, Seung Jae Hyeon4, Young-Sun Lee3, Jin Han5, Jong Hoon Jung6, Jaekwang Lee6, Hoon Ryu4,7,8, Jae-Yong Park3, Eun Mi Hwang2,*, Kyoungho Suk1,5,*
1Brain Science & Engineering Institute, Kyungpook National University, Daegu, Republic of Korea
2Center for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea
3School of Biosystems and Biomedical Sciences, College of Health Science, Korea University, Seoul, Republic of Korea
4Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea
5Department of Pharmacology and Department of Biomedical Science, School of Medicine, Kyungpook National University, Daegu, Republic of Korea
6Research Group of Functional Food Materials, Korea Food Research Institute, Wanju, Republic of Korea
7VA Boston Healthcare System, Boston, MA, USA
8Boston University Alzheimer’s Disease Center and Department of Neurology, Boston University School of Medicine, Boston, MA, USA
These authors contributed equally: Jong-Heon Kim, Hyun-Gug Jung
*Correspondence to Eun Mi Hwang or Kyoungho Suk.
Abstract
Hevin, also known as SPARC-like protein 1 (SPARCL1 or SC1), is a synaptogenic protein secreted by astrocytes and modulates the formation of glutamatergic synapses in the developing brain by interacting with synaptic adhesion proteins, such as neurexin and neuroligin. Here, we identified the neuron-specific vesicular protein calcyon as a novel interaction partner of hevin and demonstrated that this interaction played a pivotal role in synaptic reorganization after an injury in the mature brain. Astrocytic hevin was upregulated post-injury in a photothrombotic stroke model. Hevin was fragmented by MMP3 induced during the acute stage of brain injury, and this process was associated with severe gliosis. At the late stage, the functional hevin level was restored as MMP3 expression decreased. The C-terminus of hevin interacted with the N-terminus of calcyon. By using RNAi and binding competitor peptides in an ischemic brain injury model, we showed that this interaction was crucial in synaptic and functional recoveries in the sensory-motor cortex, based on histological and electrophysiological analyses. Regulated expression of hevin and calcyon and interaction between them were confirmed in a mouse model of traumatic brain injury and patients with chronic traumatic encephalopathy. Our study provides direct evidence for the causal relationship between the hevin–calcyon interaction and synaptic reorganization after brain injury. This neuron-glia interaction can be exploited to modulate synaptic reorganization under various neurological conditions.
논문정보
- Research article
- 2021년 03월 (BRIC 등록일 2021-03-29)
- 국내(교신)+국외 연구진
- 의약학 > 신경의학
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