title: Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway.
abstract: Synaptic scaling is a form of homeostatic plasticity driven by transcription-dependent changes in AMPA-type glutamate receptor (AMPAR) trafficking. To uncover the pathways involved, we performed a cell-type-specific screen for transcripts persistently altered during scaling, which identified the μ subunit (μ3A) of the adaptor protein complex AP-3A. Synaptic scaling increased μ3A (but not other AP-3 subunits) in pyramidal neurons and redistributed dendritic μ3A and AMPAR to recycling endosomes (REs). Knockdown of μ3A prevented synaptic scaling and this redistribution, while overexpression (OE) of full-length μ3A or a truncated μ3A that cannot interact with the AP-3A complex was sufficient to drive AMPAR to REs. Finally, OE of μ3A acted synergistically with GRIP1 to recruit AMPAR to the dendritic membrane. These data suggest that excess μ3A acts independently of the AP-3A complex to reroute AMPAR to RE, generating a reservoir of receptors essential for the regulated recruitment to the synaptic membrane during scaling up.
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
authors: Celine C
authors: CC
authors: Steinmetz
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
authors: Vedakumar
authors: V
authors: Tatavarty
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
authors: Ken
authors: K
authors: Sugino
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
authors: Yasuyuki
authors: Y
authors: Shima
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
authors: Anne
authors: A
authors: Joseph
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
authors: Heather
authors: H
authors: Lin
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
authors: Michael
authors: M
authors: Rutlin
authors: Department of Brain and Cognitive Science, MIT, Cambridge, MA 02139, USA.
authors: Mary
authors: M
authors: Lambo
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
authors: Chris M
authors: CM
authors: Hempel
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
authors: Benjamin W
authors: BW
authors: Okaty
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA.
authors: Suzanne
authors: S
authors: Paradis
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA. Electronic address: nelson@brandeis.edu.
authors: Sacha B
authors: SB
authors: Nelson
authors: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA. Electronic address: turrigiano@brandeis.edu.
authors: Gina G
authors: GG
authors: Turrigiano
mesh_terms: D033963:Adaptor Protein Complex 3 / Q000378:metabolism*; D033983:Adaptor Protein Complex mu Subunits / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D003712:Dendrites / Q000378:metabolism; D000074288:Discs Large Homolog 1 Protein / Q000378:metabolism; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006706:Homeostasis; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000502:physiology*; D017966:Pyramidal Cells / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics; D015854:Up-Regulation
chemical_list: D033963:Adaptor Protein Complex 3; D033983:Adaptor Protein Complex mu Subunits; D048868:Adaptor Proteins, Signal Transducing; D000074288:Discs Large Homolog 1 Protein; C000614189:Dlg1 protein, mouse; C491309:Grip1 protein, mouse; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2