MEA6 Deficiency Impairs Cerebellar Development and Motor Performance by Tethering Protein Trafficking
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Updated: Jan 22, 2026
Gait Analysis of Age-dependent Motor Impairments in Mice with Neurodegeneration
Published on: June 18, 2018
Xin-Tai Wang1, Xin-Yu Cai1, Fang-Xiao Xu1
1Department of Neurobiology, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of Medicine, Hangzhou, China.
Abstract:
Meningioma expressed antigen 6 (MEA6), also called cutaneous T cell lymphoma-associated antigen 5 (cTAGE5), was initially found in tumor tissues. MEA6 is located in endoplasmic reticulum (ER) exit sites and regulates the transport of collagen, very low density lipoprotein, and insulin. It is also reported that MEA6 might be related to Fahr's syndrome, which comprises neurological, movement, and neuropsychiatric disorders. Here, we show that MEA6 is critical to cerebellar development and motor performance. Mice with conditional knockout of MEA6 (Nestin-Cre;MEA6F/F) display smaller sizes of body and brain compared to control animals, and survive maximal 28 days after birth. Immunohistochemical and behavioral studies demonstrate that these mutant mice have defects in cerebellar development and motor performance. In contrast, PC deletion of MEA6 (pCP2-Cre;MEA6F/F) causes milder phenotypes in cerebellar morphology and motor behaviors. While pCP2-Cre;MEA6F/F mice have normal lobular formation and gait, they present the extensive self-crossing of PC dendrites and damaged motor learning. Interestingly, the expression of key molecules that participates in cerebellar development, including Slit2 and brain derived neurotrophic factor (BDNF), is significantly increased in ER, suggesting that MEA6 ablation impairs ER function and thus these proteins are arrested in ER. Our study provides insight into the roles of MEA6 in the brain and the pathogenesis of Fahr's syndrome.
Insights
Meningioma expressed antigen 6 (MEA6) is crucial for cerebellar development and motor control. Its absence impairs brain growth and motor learning, potentially linking MEA6 to neurological disorders like Fahr's syndrome.
Area of Science:
- Neuroscience
- Developmental Biology
- Molecular Biology
Background:
- Meningioma expressed antigen 6 (MEA6), also known as cutaneous T cell lymphoma-associated antigen 5 (cTAGE5), is found in ER exit sites and regulates protein transport.
- MEA6's potential involvement in Fahr's syndrome, a disorder affecting neurological, movement, and psychiatric functions, has been suggested.
- The precise role of MEA6 in brain development and function remains largely unexplored.
Purpose of the Study:
- To investigate the role of MEA6 in cerebellar development and motor performance.
- To elucidate the cellular and molecular mechanisms underlying MEA6's function in the brain.
- To explore the potential link between MEA6 dysfunction and Fahr's syndrome pathogenesis.
Main Methods:
- Generation of conditional MEA6 knockout mouse models (Nestin-Cre;MEA6F/F and pCP2-Cre;MEA6F/F).
- Phenotypic analysis including body and brain size measurements, immunohistochemistry, and behavioral tests (motor performance, motor learning).
- Analysis of protein expression and localization within the endoplasmic reticulum (ER).
Main Results:
- Conditional knockout of MEA6 in neural progenitors (Nestin-Cre;MEA6F/F) resulted in smaller body and brain size, reduced survival, and severe defects in cerebellar development and motor performance.
- Purkinje cell-specific deletion of MEA6 (pCP2-Cre;MEA6F/F) led to milder phenotypes, including normal gait but impaired motor learning and aberrant Purkinje cell dendrite morphology.
- MEA6 ablation caused ER retention of key developmental molecules like Slit2 and brain-derived neurotrophic factor (BDNF), indicating impaired ER function.
Conclusions:
- MEA6 is essential for normal cerebellar development and motor function.
- MEA6 deficiency disrupts ER-mediated protein transport, impacting cerebellar development and motor learning.
- These findings highlight MEA6's critical role in the brain and offer insights into the pathogenesis of Fahr's syndrome.
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