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Lookup NU author(s): Dr Ana TopfORCiD
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0).
© 2019 Oury et al. Complex mechanisms are required to form neuromuscular synapses, direct their subsequent maturation, and maintain the synapse throughout life. Transcriptional and post-translational pathways play important roles in synaptic differentiation and direct the accumulation of the neurotransmitter receptors, acetylcholine receptors (AChRs), to the postsynaptic membrane, ensuring for reliable synaptic transmission. Rapsyn, an intracellular peripheral membrane protein that binds AChRs, is essential for synaptic differentiation, but how Rapsyn acts is poorly understood. We screened for proteins that coisolate with AChRs in a Rapsyn-dependent manner and show that microtubule actin cross linking factor 1 (MACF1), a scaffolding protein with binding sites for microtubules (MT) and actin, is concentrated at neuromuscular synapses, where it binds Rapsyn and serves as a synaptic organizer for MT-associated proteins, EB1 and MAP1b, and the actin-associated protein, Vinculin. MACF1 plays an important role in maintaining synaptic differentiation and efficient synaptic transmission in mice, and variants in MACF1 are associated with congenital myasthenia in humans.
Author(s): Oury J, Liu Y, Topf A, Todorovic S, Hoedt E, Preethish-Kumar V, Neubert TA, Lin W, Lochmuller H, Burden SJ
Publication type: Article
Publication status: Published
Journal: Journal of Cell Biology
Year: 2019
Volume: 218
Issue: 5
Pages: 1686-1705
Print publication date: 06/05/2019
Online publication date: 06/03/2019
Acceptance date: 07/02/2019
Date deposited: 29/05/2019
ISSN (print): 0021-9525
ISSN (electronic): 1540-8140
Publisher: Rockefeller University Press
URL: https://doi.org/10.1083/jcb.201810023
DOI: 10.1083/jcb.201810023
PubMed id: 30842214
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