Cd99l2 regulates excitatory synapse development and restrains immediate-early gene activation
Minji Kang1, Sang Ho Yoon2, Minkyung Kang2
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea; Neuroscience Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea; Transplantation Research Institute, Medical Research Center, Seoul National University, Seoul 03080, South Korea.
Cell Reports
|January 14, 2025
Summary
Cd99 molecule-like 2 (Cd99l2) in neurons promotes neurite outgrowth and synapse development. This protein inhibits neuronal activation by regulating immediate-early genes, impacting learning and memory.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Cd99 molecule-like 2 (Cd99l2) is a type I transmembrane protein with known roles in leukocyte transmigration.
- Despite high expression in the brain, its specific function in neurons remained largely unknown.
Purpose of the Study:
- To elucidate the role of Cd99l2 in neuronal function, focusing on its impact on neurite outgrowth, synapse development, and neuronal activity.
Main Methods:
- Investigated Cd99l2 expression in neurons.
- Examined the effect of Cd99l2 on neurite outgrowth and excitatory synapse development.
- Assessed the regulation of immediate-early genes (IEGs) and transcription factors (CREB, SRF) by Cd99l2.
- Utilized Cd99l2 knockout mice to study synaptic transmission, plasticity, and behavioral deficits.
Main Results:
- Cd99l2 is primarily expressed in neurons and positively regulates neurite outgrowth and excitatory synapse formation.
- Cd99l2 inhibits the activity of transcription factors CREB and SRF, inversely regulating IEG expression (Arc, Egr1, c-Fos).
- Neuronal inactivation enhances cell surface transport of Cd99l2, strengthening its inhibitory signaling.
- Cd99l2 knockout mice showed impaired hippocampal synaptic function, spatial memory, and fear conditioning.
Conclusions:
- Neuronal Cd99l2 acts as a synaptic cell adhesion molecule that negatively controls neuronal activation.
- Cd99l2 plays a critical role in regulating synaptic plasticity, learning, and memory formation.
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