title: Adaptor Complex 2 Controls Dendrite Morphology via mTOR-Dependent Expression of GluA2.
abstract: The formation of dendritic arbors in neurons is a highly regulated process. Among the regulators of dendritogenesis are numerous membrane proteins that are eventually internalized via clathrin-mediated endocytosis. AP2 is an adaptor complex that is responsible for recruiting endocytic machinery to internalized cargo. Its direct involvement in dendritogenesis in mammalian neurons has not yet been tested. We found that the knockdown of AP2b1 (β2-adaptin), an AP2 subunit, reduced the number of dendrites in developing rat hippocampal neurons and decreased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA2 levels by inhibiting mechanistic/mammalian target of rapamycin (mTOR). The dendritic tree abruption that was caused by AP2b1 knockdown was rescued by the overexpression of GluA2 or restoration of the activity of the mTOR effector p70S6 kinase (S6K1). Altogether, this work provides evidence that the AP2 adaptor complex is needed for the dendritogenesis of mammalian neurons and reveals that mTOR-dependent GluA2 biosynthesis contributes to this process.
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Koscielny
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Malik
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Liszewska
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Zmorzynska
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Tempes
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Tarkowski
authors.affiliation: Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland. jaworski@iimcb.gov.pl.
authors.forename: Jacek
authors.initials: J
authors.lastname: Jaworski
mesh_terms: D033962:Adaptor Protein Complex 2 / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D048430:Cell Shape / Q000502:physiology; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D033962:Adaptor Protein Complex 2; D018091:Receptors, AMPA; D058570:TOR Serine-Threonine Kinases; C104722:glutamate receptor ionotropic, AMPA 2
keywords: AP2b1; Dendritic arbor; GluA2; mTOR