title: Clathrin-independent trafficking of AMPA receptors.
abstract: Membrane trafficking of AMPA receptors (AMPARs) is critical for neuronal function and plasticity. Although rapid forms of AMPAR internalization during long-term depression (LTD) require clathrin and dynamin, the mechanisms governing constitutive AMPAR turnover and internalization of AMPARs during slow homeostatic forms of synaptic plasticity remain unexplored. Here, we show that, in contrast to LTD, constitutive AMPAR internalization and homeostatic AMPAR downscaling in rat neurons do not require dynamin or clathrin function. Instead, constitutive AMPAR trafficking is blocked by a Rac1 inhibitor and is regulated by a dynamic nonstructural pool of F-actin. Our findings reveal a novel role for neuronal clathrin-independent endocytosis controlled by actin dynamics and suggest that the interplay between different modes of receptor endocytosis provides for segregation between distinct modes of neuronal plasticity.
authors: Schools of Biochemistry and Wolfson Centre for Age-Related Diseases, King's College London, London SE1 1UL, United Kingdom oleg.glebov@kcl.ac.uk anjmh@bristol.ac.uk.
authors: Oleg O
authors: OO
authors: Glebov
authors: Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, University of Bristol, Bristol BS8 1TD, United Kingdom, and.
authors: Cezar M
authors: CM
authors: Tigaret
authors: Physiology and Pharmacology, Medical Research Council Centre for Synaptic Plasticity, University of Bristol, Bristol BS8 1TD, United Kingdom, and.
authors: Jack R
authors: JR
authors: Mellor
authors: Schools of Biochemistry and oleg.glebov@kcl.ac.uk anjmh@bristol.ac.uk.
authors: Jeremy M
authors: JM
authors: Henley
mesh_terms: D000199:Actins / Q000378:metabolism*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D018929:Cell Culture Techniques; D002966:Clathrin / Q000037:antagonists & inhibitors / Q000378:metabolism; D034281:Dynamins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology; D006835:Hydrazones / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D000199:Actins; D000634:Aminoquinolines; D002966:Clathrin; D006835:Hydrazones; C511794:N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide; C487513:NSC 23766; D011743:Pyrimidines; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein; D034281:Dynamins
keywords: AMPA receptors; endocytosis; membrane trafficking; synaptic plasticity