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Stonin 2 Is a major adaptor protein for clathrin-mediated synaptic vesicle retrieval

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Willox, Anna K. and Royle, Stephen J. (2012) Stonin 2 Is a major adaptor protein for clathrin-mediated synaptic vesicle retrieval. Current Biology, 22 (15). pp. 1435-1439. doi:10.1016/j.cub.2012.05.048

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Official URL: http://dx.doi.org/10.1016/j.cub.2012.05.048

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Abstract

At small synapses in the brain, clathrin-mediated endocytosis (CME) is the dominant mode of synaptic vesicle retrieval following weak stimulation [1,2,3,4]. Clathrin cannot bind to membranes or cargo directly and instead uses adaptor proteins to do so [5]. Although the involvement of clathrin and dynamin in synaptic vesicle retrieval is clear, it is unknown which adaptor proteins are used to sort the essential components into the vesicle [1,4,6]. In nonneuronal cells, CME of the majority of transmembrane receptors is either directly or indirectly via the heterotetrameric AP-2 complex [5]. In neurons, RNAi of the μ2 subunit of AP-2 resulted in only minor inhibition of synaptic vesicle retrieval [7,8], a result echoed in C. elegans [9]. These results suggest that alternative adaptors may be employed for vesicle retrieval. Here, we tested which adaptors are required for vesicle retrieval at hippocampal synapses using a targeted RNAi screen coupled with optical measurements. Stonin 2 emerged as a major adaptor, whereas AP-2 played only a minor role in endocytosis at the synapse. Moreover, using chemically induced rerouting of stonin 2 to mitochondria it was possible to switch endocytically competent synapses to an impaired state on a timescale of minutes.

Item Type: Journal Article
Divisions: Faculty of Medicine > Warwick Medical School
Journal or Publication Title: Current Biology
Publisher: Cell Press
ISSN: 0960-9822
Official Date: 21 June 2012
Dates:
DateEvent
21 June 2012Published
Volume: 22
Number: 15
Page Range: pp. 1435-1439
DOI: 10.1016/j.cub.2012.05.048
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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