Neurodevelopment is essential for the formation of neuronal networks and normal brain function.
previous studies by Xu Deheng, Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences, cTAGE5/MEA6 is involved in regulating the transport process and secretion of ultra-low density lipoproteins from endosomein networks to Gorky (Cell Research 2016) in the liver, regulating the transport of insulin progenitors and the secretion of insulin (J Cell Biology) in the pancreas, but its role in the transport of non-secreted components and brain development is unclear.
team members found severe defects in neurodevelopment caused by conditions in the brain that knock edited cTAGE5/MEA6, including growth, formation and maintenance of neuronal dendris and synapses, astrocyte activation, and animal abnormal behavior.
at the same time, it is revealed that the absence of cTAGE5/MEA6 affects the interaction between COPII components, SAR1 and SEC23, resulting in the continuous activation of SAR1, COPII vesicle formation and the internal network to the Gorky body material transport abnormalities, thus disrupting the transport of the membrane components of neurons.
these defects affect not only the transport of the substances needed for dendritic and burst-triggering, but also the signaling pathways needed for neuronal development.
the mutation in cTAGE5/MEA6 was found in patients with Fahr disease, and the study provides insight into the pathogenesis of the disease.
the findings were published online September 17 in the Proceedings of the National Academy of Sciences (PNAS, DOI: 10.1073/pnas.1804083115). Zhang Feng, a doctoral student in the
Xu Deheng Research Group, and Wang Yaqing, an associate researcher, are the co-first authors of the paper.
the research is supported by the National Natural Science Foundation of China and the Chinese Academy of Sciences.