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

Cell Reports (Sep 2016)

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

Affiliations

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
Gina G. Turrigiano: Department of Biology and Center for Behavioral Genomics, Brandeis University, Waltham, MA 02454, USA

DOI: https://doi.org/10.1016/j.celrep.2016.08.009
Journal volume & issue: Vol. 16, no. 10
pp. 2711 – 2722

Abstract

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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.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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