Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway

Celine C Steinmetz; Vedakumar Tatavarty; Ken Sugino; Yasuyuki Shima; Anne Joseph; Heather Lin; Michael Rutlin; Mary Lambo; Chris M Hempel; Benjamin W Okaty; Suzanne Paradis; Sacha B Nelson; Gina G Turrigiano

doi:10.1016/j.celrep.2016.08.009

Back

Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway

Journal article

Open access

Peer reviewed

Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway

Celine C Steinmetz, Vedakumar Tatavarty, Ken Sugino, Yasuyuki Shima, Anne Joseph, Heather Lin, Michael Rutlin, Mary Lambo, Chris M Hempel, Benjamin W Okaty, …

Cell reports (Cambridge), Vol.16(10), pp.2711-2722

09/06/2016

DOI: https://doi.org/10.1016/j.celrep.2016.08.009

PMID: 27568566

Abstract

Dendrites - metabolism

Pyramidal Cells - metabolism

Up-Regulation

Adaptor Protein Complex mu Subunits - metabolism

Homeostasis

Transcriptome - genetics

Adaptor Protein Complex 3 - metabolism

Endosomes - metabolism

Gene Knockdown Techniques

Nerve Tissue Proteins - metabolism

Discs Large Homolog 1 Protein - metabolism

Endocytosis

Animals

Neuronal Plasticity - physiology

Synapses - metabolism

Mice

Adaptor Proteins, Signal Transducing - metabolism

Receptors, AMPA - metabolism

Neuroscience

Synaptic Transmission

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.

Files and links (1)

url

https://doi.org/10.1016/j.celrep.2016.08.009View

Published (Version of record) Open

Metrics

34 Record Views

See more details

Details

Title: Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway
Creators: Celine C Steinmetz - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
Vedakumar Tatavarty - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
Ken Sugino - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
Yasuyuki Shima - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
Anne Joseph - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
Heather Lin - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
Michael Rutlin - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
Mary Lambo - Department of Brain and Cognitive Science, MIT, Cambridge, MA 02139, USA
Chris M Hempel - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
Benjamin W Okaty - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
Suzanne Paradis - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA
Sacha B Nelson - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA. Electronic address: nelson@brandeis.edu
Gina G Turrigiano - Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA. Electronic address: turrigiano@brandeis.edu
Publication Details: Cell reports (Cambridge), Vol.16(10), pp.2711-2722
Publisher: United States
Grant note: R01 EY022360 / NEI NIH HHS R01 NS065856 / NINDS NIH HHS R37 NS092635 / NINDS NIH HHS S10 RR031531 / NCRR NIH HHS P01 NS079419 / NINDS NIH HHS T32 NS007292 / NINDS NIH HHS
Identifiers: 9923957826801921
Academic Unit: Department of Biology; Benjamin and Mae Volen National Center for Complex Systems; Interdepartmental Program in Neuroscience
Language: English
Resource Type: Journal article

Upregulation of μ3A Drives Homeostatic Plasticity by Rerouting AMPAR into the Recycling Endosomal Pathway

Abstract

Files and links (1)

Metrics

Details

Brandeis University Social media