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| Subject Categories: Membranes & Transport | Neuroscience |
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| The EMBO Journal
(2003) 22, 558–568, doi:10.1093/emboj/cdg059 |
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| Regulated delivery of AMPA receptor subunits to the presynaptic membrane |
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| Ursula Schenk1, Claudia Verderio1, Fabio Benfenati2 and Michela Matteoli1 |
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1 CNR Institute of Neuroscience, Cellular and Molecular Pharmacology, Center of Excellence for Neurodegenerative Diseases, Department of Medical Pharmacology, via Vanvitelli 32, 20129 Milano Italy 2 Department of Experimental Medicine, Section of Physiology, University of Genova, Viale Benedetto XV 3, 16132 Genova, Italy To whom correspondence should be addressed Michela Matteoli, MichelaM@csfic.mi.cnr.it Received 24 July 2002; Revised 24 October 2002; Accepted 4 December 2002. |
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| Abstract |
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In recent years, a role for AMPA receptors as modulators of presynaptic functions has emerged. We have investigated the presence of AMPA receptor subunits and the possible dynamic control of their surface exposure at the presynaptic membrane. We demonstrate that the AMPA receptor subunits GluR1 and GluR2 are expressed and organized in functional receptors in axonal growth cones of hippocampal neurons. AMPA receptors are actively internalized upon activation and recruited to the surface upon depolarization. Pretreatment of cultures with botulinum toxin E or tetanus toxin prevents the receptor insertion into the plasma membrane, whereas treatment with  -latrotoxin enhances the surface exposure of GluR2, both in growth cones of cultured neurons and in brain synaptosomes. Purification of small synaptic vesicles through controlled-pore glass chromatography, revealed that both GluR2 and GluR1, but not the GluR2 interacting protein GRIP, copurify with synaptic vesicles. These data indicate that, at steady state, a major pool of AMPA receptor subunits reside in synaptic vesicle membranes and can be recruited to the presynaptic membrane as functional receptors in response to depolarization. |
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| Keywords: AMPA, GluR1, GluR2, growth cone, synaptic vesicles |
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