{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yang R"],"funding":["George Barth Geller Professorship","NICHD NIH HHS","NCATS NIH HHS","Howard Hughes Medical Institute","NIMH NIH HHS","Office of Extramural Research, National Institutes of Health","NINDS NIH HHS"],"pagination":["19717-19726"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6765234"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["116(39)"],"pubmed_abstract":["Giant ankyrin-G (gAnkG) coordinates assembly of axon initial segments (AISs), which are sites of action potential generation located in proximal axons of most vertebrate neurons. Here, we identify a mechanism required for normal neural development in humans that ensures ordered recruitment of gAnkG and β4-spectrin to the AIS. We identified 3 human neurodevelopmental missense mutations located in the neurospecific domain of gAnkG that prevent recruitment of β4-spectrin, resulting in a lower density and more elongated pattern for gAnkG and its partners than in the mature AIS. We found that these mutations inhibit transition of gAnkG from a closed configuration with close apposition of N- and C-terminal domains to an extended state that is required for binding and recruitment of β4-spectrin, "],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly."],"pmcid":["PMC6765234"],"funding_grant_id":["F31NS096848","not applicable","R21 MH115155","F31 NS096848","R01 MH098114","UL1 TR001863","R21 HD087795","R01 MH117289","R21 MH104316","R21MH115155"],"pubmed_authors":["Fernandez-Jaen A","Walder-Christensen KK","Garcia-Prieto ID","Lalani S","Yang R","Speltz L","Bennett V","Jiang YH","Yan H","Alvarez S"],"additional_accession":[]},"is_claimable":false,"name":"Neurodevelopmental mutation of giant ankyrin-G disrupts a core mechanism for axon initial segment assembly.","description":"Giant ankyrin-G (gAnkG) coordinates assembly of axon initial segments (AISs), which are sites of action potential generation located in proximal axons of most vertebrate neurons. Here, we identify a mechanism required for normal neural development in humans that ensures ordered recruitment of gAnkG and β4-spectrin to the AIS. We identified 3 human neurodevelopmental missense mutations located in the neurospecific domain of gAnkG that prevent recruitment of β4-spectrin, resulting in a lower density and more elongated pattern for gAnkG and its partners than in the mature AIS. We found that these mutations inhibit transition of gAnkG from a closed configuration with close apposition of N- and C-terminal domains to an extended state that is required for binding and recruitment of β4-spectrin, ","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Sep","modification":"2026-05-07T05:52:17.962Z","creation":"2019-10-11T07:12:33Z"},"accession":"S-EPMC6765234","cross_references":{"pubmed":["31451636"],"doi":["10.1073/pnas.1909989116"]}}