Structure and superorganization of acetylcholine receptor-rapsyn complexes
Publisher DOI
PubMed ID
23754381
Abstract
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.
Date Issued
2013-06-25
Publication Type
Article
Subject(s)
Subjects
cryoelectron microscopy ligand-gated ion channel neurotransmitter receptor clustering synapse tetratricopeptide repeat
Language(s)
en
Author(s)
Unwin, Nigel |
Additional Credits
Journal
Proceedings of the National Academy of Sciences of the United States of America - PNAS
Publisher
National Academy of Sciences NAS
ISSN
0027-8424
Access(Rights)
restricted