8htt
Cryo-EM structure of human TMEM87A, gluconate-boundCryo-EM structure of human TMEM87A, gluconate-bound
Structural highlights
FunctionTM87A_HUMAN May be involved in retrograde transport from endosomes to the trans-Golgi network (TGN) (PubMed:26157166). In one study, shown to be a component of a novel mechanoelectrical transduction pathway which is involved in cell adhesion and migration, and is thought to act either as a mechanically activated ion channel or as an accessory protein which modulates an unidentified mechanically activated ion channel (PubMed:32228863). In another study, neither basal nor mechanically activated channel activity has been observed and, based on structural similarity with WLS, has been suggested to function as a trafficking chaperone for membrane-associated cargo (PubMed:36373655).[1] [2] [3] Publication Abstract from PubMedImpaired ion channels regulating Golgi pH lead to structural alterations in the Golgi apparatus, such as fragmentation, which is found, along with cognitive impairment, in Alzheimer's disease. However, the causal relationship between altered Golgi structure and cognitive impairment remains elusive due to the lack of understanding of ion channels in the Golgi apparatus of brain cells. Here, we identify that a transmembrane protein TMEM87A, renamed Golgi-pH-regulating cation channel (GolpHCat), expressed in astrocytes and neurons that contributes to hippocampus-dependent memory. We find that GolpHCat displays unique voltage-dependent currents, which is potently inhibited by gluconate. Additionally, we gain structural insights into the ion conduction through GolpHCat at the molecular level by determining three high-resolution cryogenic-electron microscopy structures of human GolpHCat. GolpHCat-knockout mice show fragmented Golgi morphology and altered protein glycosylation and functions in the hippocampus, leading to impaired spatial memory. These findings suggest a molecular target for Golgi-related diseases and cognitive impairment. GolpHCat (TMEM87A), a unique voltage-dependent cation channel in Golgi apparatus, contributes to Golgi-pH maintenance and hippocampus-dependent memory.,Kang H, Han AR, Zhang A, Jeong H, Koh W, Lee JM, Lee H, Jo HY, Maria-Solano MA, Bhalla M, Kwon J, Roh WS, Yang J, An HJ, Choi S, Kim HM, Lee CJ Nat Commun. 2024 Jul 11;15(1):5830. doi: 10.1038/s41467-024-49297-8. PMID:38992057[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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