PICK1 Regulates AMPA Receptor Endocytosis Via Direct Interactions with AP2 α-appendage and Dynamin

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2017 Sep 1

PMID 28855251

Citations 32

Authors

Maria Fiuza

Christine M Rostosky

Gabrielle T Parkinson

Alexei M Bygrave

Nagaraj Halemani

Marcio Baptista

Ira Milosevic

Jonathan G Hanley

Affiliations

Soon will be listed here.

Abstract

Clathrin-mediated endocytosis (CME) is used to internalize a diverse range of cargo proteins from the cell surface, often in response to specific signals. In neurons, the rapid endocytosis of GluA2-containing AMPA receptors (AMPARs) in response to NMDA receptor (NMDAR) stimulation causes a reduction in synaptic strength and is the central mechanism for long-term depression, which underlies certain forms of learning. The mechanisms that link NMDAR activation to CME of AMPARs remain elusive. PICK1 is a BAR domain protein required for NMDAR-dependent reductions in surface GluA2; however, the molecular mechanisms involved are unclear. In this study, we show that PICK1 makes direct, NMDAR-dependent interactions with the core endocytic proteins AP2 and dynamin. PICK1-AP2 interactions are required for clustering AMPARs at endocytic zones in dendrites in response to NMDAR stimulation and for consequent AMPAR internalization. We further show that PICK1 stimulates dynamin polymerization. We propose that PICK1 is a cargo-specific endocytic accessory protein required for efficient, activity-dependent AMPAR endocytosis.

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References

Beattie E, Carroll R, Yu X, Morishita W, Yasuda H, von Zastrow M . Regulation of AMPA receptor endocytosis by a signaling mechanism shared with LTD. Nat Neurosci. 2000; 3(12):1291-300. DOI: 10.1038/81823. View

Rocca D, Amici M, Antoniou A, Blanco Suarez E, Halemani N, Murk K . The small GTPase Arf1 modulates Arp2/3-mediated actin polymerization via PICK1 to regulate synaptic plasticity. Neuron. 2013; 79(2):293-307. PMC: 3725416. DOI: 10.1016/j.neuron.2013.05.003. View

Banke T, Bowie D, Lee H, Huganir R, Schousboe A, Traynelis S . Control of GluR1 AMPA receptor function by cAMP-dependent protein kinase. J Neurosci. 2000; 20(1):89-102. PMC: 6774102. View

Ferguson S, Ferguson S, Raimondi A, Paradise S, Shen H, Mesaki K . Coordinated actions of actin and BAR proteins upstream of dynamin at endocytic clathrin-coated pits. Dev Cell. 2010; 17(6):811-22. PMC: 2861561. DOI: 10.1016/j.devcel.2009.11.005. View

Lee S, Simonetta A, Sheng M . Subunit rules governing the sorting of internalized AMPA receptors in hippocampal neurons. Neuron. 2004; 43(2):221-36. DOI: 10.1016/j.neuron.2004.06.015. View

Traub L . Tickets to ride: selecting cargo for clathrin-regulated internalization. Nat Rev Mol Cell Biol. 2009; 10(9):583-96. DOI: 10.1038/nrm2751. View

Migues P, Liu L, Archbold G, Einarsson E, Wong J, Bonasia K . Blocking Synaptic Removal of GluA2-Containing AMPA Receptors Prevents the Natural Forgetting of Long-Term Memories. J Neurosci. 2016; 36(12):3481-94. PMC: 6601735. DOI: 10.1523/JNEUROSCI.3333-15.2016. View

Kastning K, Kukhtina V, Kittler J, Chen G, Pechstein A, Enders S . Molecular determinants for the interaction between AMPA receptors and the clathrin adaptor complex AP-2. Proc Natl Acad Sci U S A. 2007; 104(8):2991-6. PMC: 1815294. DOI: 10.1073/pnas.0611170104. View

Dixon R, Mellor J, Hanley J . PICK1-mediated glutamate receptor subunit 2 (GluR2) trafficking contributes to cell death in oxygen/glucose-deprived hippocampal neurons. J Biol Chem. 2009; 284(21):14230-5. PMC: 2682871. DOI: 10.1074/jbc.M901203200. View

10.

Blanpied T, Scott D, Ehlers M . Dynamics and regulation of clathrin coats at specialized endocytic zones of dendrites and spines. Neuron. 2002; 36(3):435-49. DOI: 10.1016/s0896-6273(02)00979-0. View

11.

Taylor M, Perrais D, Merrifield C . A high precision survey of the molecular dynamics of mammalian clathrin-mediated endocytosis. PLoS Biol. 2011; 9(3):e1000604. PMC: 3062526. DOI: 10.1371/journal.pbio.1000604. View

12.

Ball C, Hunt S, Robinson M . Expression and localization of alpha-adaptin isoforms. J Cell Sci. 1995; 108 ( Pt 8):2865-75. DOI: 10.1242/jcs.108.8.2865. View

13.

Iwakura Y, Nagano T, Kawamura M, Horikawa H, Ibaraki K, Takei N . N-methyl-D-aspartate-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) receptor down-regulation involves interaction of the carboxyl terminus of GluR2/3 with Pick1. Ligand-binding studies using Sindbis vectors carrying AMPA.... J Biol Chem. 2001; 276(43):40025-32. DOI: 10.1074/jbc.M103125200. View

14.

Robinson M . Adaptable adaptors for coated vesicles. Trends Cell Biol. 2004; 14(4):167-74. DOI: 10.1016/j.tcb.2004.02.002. View

15.

Anggono V, Huganir R . Regulation of AMPA receptor trafficking and synaptic plasticity. Curr Opin Neurobiol. 2012; 22(3):461-9. PMC: 3392447. DOI: 10.1016/j.conb.2011.12.006. View

16.

Man H, Lin J, Ju W, Ahmadian G, Liu L, Becker L . Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization. Neuron. 2000; 25(3):649-62. DOI: 10.1016/s0896-6273(00)81067-3. View

17.

Barylko B, Binns D, Lin K, Atkinson M, Jameson D, Yin H . Synergistic activation of dynamin GTPase by Grb2 and phosphoinositides. J Biol Chem. 1998; 273(6):3791-7. DOI: 10.1074/jbc.273.6.3791. View

18.

Soulet F, Yarar D, Leonard M, Schmid S . SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis. Mol Biol Cell. 2005; 16(4):2058-67. PMC: 1073683. DOI: 10.1091/mbc.e04-11-1016. View

19.

Bell J, Park E, Ai J, Baker A . PICK1-mediated GluR2 endocytosis contributes to cellular injury after neuronal trauma. Cell Death Differ. 2009; 16(12):1665-80. DOI: 10.1038/cdd.2009.106. View

20.

Matsuda S, Kakegawa W, Budisantoso T, Nomura T, Kohda K, Yuzaki M . Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression. Nat Commun. 2013; 4:2759. DOI: 10.1038/ncomms3759. View