title: Adaptor Protein 2 (AP-2) complex is essential for functional axogenesis in hippocampal neurons.
abstract: The complexity and diversity of a neural network requires regulated elongation and branching of axons, as well as the formation of synapses between neurons. In the present study we explore the role of AP-2, a key endocytic adaptor protein complex, in the development of rat hippocampal neurons. We found that the loss of AP-2 during the early stage of development resulted in impaired axon extension and failed maturation of the axon initial segment (AIS). Normally the AIS performs two tasks in concert, stabilizing neural polarity and generating action potentials. In AP-2 silenced axons polarity is established, however there is a failure to establish action potential firing. Consequently, this impairs activity-driven Ca2+influx and exocytosis at nerve terminals. In contrast, removal of AP-2 from older neurons does not impair axonal growth or signaling and synaptic function. Our data reveal that AP-2 has important roles in functional axogenesis by proper extension of axon as well as the formation of AIS during the early step of neurodevelopment.
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, South Korea.
authors.forename: Jae Won
authors.initials: JW
authors.lastname: Kyung
authors.affiliation: Department of Biology, Molecular Cellular Biology Program, Dartmouth College, Hanover, NH, 03755, USA.
authors.forename: In Ha
authors.initials: IH
authors.lastname: Cho
authors.affiliation: Laboratory of Molecular Cancer Therapeutics, Scripps Korea Antibody Institute, Chuncheon, 24341, South Korea.
authors.forename: Sukmook
authors.initials: S
authors.lastname: Lee
authors.affiliation: School of Life Science, Bioimaging Research Center, Gwangju Institute of Science and Technology (GIST), Gwangju, 61005, South Korea.
authors.forename: Woo Keun
authors.initials: WK
authors.lastname: Song
authors.affiliation: Department of Biochemistry, Weill Cornell Medical College, New York, NY, 10065, USA.
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Ryan
authors.affiliation: Department of Biology, Molecular Cellular Biology Program, Dartmouth College, Hanover, NH, 03755, USA.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Hoppa
authors.affiliation: Department of Biomedical Science, Graduate School, Kyung Hee University, Seoul, 02447, South Korea.|Department of Physiology, Neurodegeneration Control Research Center, School of Medicine, Kyung Hee University, Seoul, 02447, South Korea.
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000200:Action Potentials; D033962:Adaptor Protein Complex 2 / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism*; D015415:Biomarkers; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D008954:Models, Biological; D017966:Pyramidal Cells / Q000166:cytology* / Q000502:physiology*; D051381:Rats; D013569:Synapses / Q000235:genetics / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism
chemical_list: D033962:Adaptor Protein Complex 2; D015415:Biomarkers; D002118:Calcium