Structure and superorganization of acetylcholine receptor-rapsyn complexes

Zuber, Benoît; Unwin, Nigel (2013). Structure and superorganization of acetylcholine receptor-rapsyn complexes. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 110(26), pp. 10622-10627. National Academy of Sciences NAS 10.1073/pnas.1301277110

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The scaffolding protein at the neuromuscular junction, rapsyn, enables clustering of nicotinic acetylcholine receptors in high concentration and is critical for muscle function. Patients with insufficient receptor clustering suffer from muscle weakness. However, the detailed organization of the receptor-rapsyn network is poorly understood: it is unclear whether rapsyn first forms a wide meshwork to which receptors can subsequently dock or whether it only forms short bridges linking receptors together to make a large cluster. Furthermore, the number of rapsyn-binding sites per receptor (a heteropentamer) has been controversial. Here, we show by cryoelectron tomography and subtomogram averaging of Torpedo postsynaptic membrane that receptors are connected by up to three rapsyn bridges, the minimum number required to form a 2D network. Half of the receptors belong to rapsyn-connected groups comprising between two and fourteen receptors. Our results provide a structural basis for explaining the stability and low diffusion of receptors within clusters.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy

UniBE Contributor:

Zuber, Benoît

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0027-8424

Publisher:

National Academy of Sciences NAS

Language:

English

Submitter:

Benoît Zuber

Date Deposited:

20 Mar 2014 20:30

Last Modified:

16 Apr 2015 06:32

Publisher DOI:

10.1073/pnas.1301277110

PubMed ID:

23754381

Uncontrolled Keywords:

cryoelectron microscopy ligand-gated ion channel neurotransmitter receptor clustering synapse tetratricopeptide repeat

BORIS DOI:

10.7892/boris.46870

URI:

https://boris.unibe.ch/id/eprint/46870

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