Phospholipid flippases ATP8A1 and ATP8A2 regulate GABAA receptor trafficking through distinct mechanisms in hippocampal neurons. M Kawase et al.
Description
Research Overview : Phospholipid asymmetry in cellular membranes is maintained by flippases. ATP8A1 and ATP8A2 are the principal flippases of phosphatidylserine (PS) in the mammalian nervous system; however, their specific physiological roles and potential functional redundancy remain incompletely characterized. Here we show that ATP8A1/ATP8A2 double-knockout mice displayed more severe growth retardation than ATP8A2 knockout mice, indicating that ATP8A1 and ATP8A2 play redundant roles. In hippocampal neurons, ATP8A2 was highly enriched at inhibitory post-synapses. Surface biotinylation assays revealed increased surface GABAA receptor levels of hippocampal neurons deficient for ATP8A1 or ATP8A2. Mechanistically, our data support a model in which ATP8A2, but not ATP8A1, regulates local membrane lipid asymmetry, thereby facilitating dynamin2 recruitment and promoting GABAA receptor endocytosis. Collectively, ATP8A1 and ATP8A2 share overlapping roles in postnatal growth while they contribute to neural function by modulating inhibitory synaptic transmission through distinct mechanisms. Dataset Contents : This dataset contains the original, uncropped, and unmodified raw data associated with the study.
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Institutions
- Nagoya City UniversityAichi, Nagoya
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Funders
- Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and TechnologyTokyo
- Nagoya City UniversityNagoya
- Terumo (Japan)Tokyo