| First Author | Akamine S | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 12 | Pages | 16601-16621 |
| PubMed ID | 33107105 | Mgi Jnum | J:306185 |
| Mgi Id | MGI:6705467 | Doi | 10.1096/fj.202001113R |
| Citation | Akamine S, et al. (2020) GNAO1 organizes the cytoskeletal remodeling and firing of developing neurons. FASEB J 34(12):16601-16621 |
| abstractText | Developmental and epileptic encephalopathy (DEE) represents a group of neurodevelopmental disorders characterized by infantile-onset intractable seizures and unfavorable prognosis of psychomotor development. To date, hundreds of genes have been linked to the onset of DEE. GNAO1 is a DEE-associated gene encoding the alpha-O1 subunit of guanine nucleotide-binding protein (GalphaO ). Despite the increasing number of reported children with GNAO1 encephalopathy, the molecular mechanisms underlying their neurodevelopmental phenotypes remain elusive. We herein present that co-immunoprecipitation and mass spectrometry analyses identified another DEE-associated protein, SPTAN1, as an interacting partner of GalphaO . Silencing of endogenous Gnao1 attenuated the neurite outgrowth and calcium-dependent signaling. Inactivation of GNAO1 in human-induced pluripotent stem cells gave rise to anomalous brain organoids that only weakly expressed SPTAN1 and Ankyrin-G. Furthermore, GNAO1-deficient organoids failed to conduct synchronized firing to adjacent neurons. These data indicate that GalphaO and other DEE-associated proteins organize the cytoskeletal remodeling and functional polarity of neurons in the developing brain. |
