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MACF1 links rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses

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.

Publication metadata

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


DOI: 10.1083/jcb.201810023

PubMed id: 30842214


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Funder referenceFunder name
P30 NS050276
RO1 NS055028
RO1 NS075124