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

Julien Oury, Yun Liu, Ana Töpf, Slobodanka Todorovic, Esthelle Hoedt, Veeramani Preethish-Kumar, Thomas A. Neubert, Weichun Lin, Hanns Lochmüller, Steven J. Burden

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1686-1705
Number of pages20
JournalJournal of Cell Biology
Volume218
Issue number5
DOIs
StatePublished - May 1 2019

ASJC Scopus subject areas

  • Cell Biology

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    Oury, J., Liu, Y., Töpf, A., Todorovic, S., Hoedt, E., Preethish-Kumar, V., Neubert, T. A., Lin, W., Lochmüller, H., & Burden, S. J. (2019). MACF1 links rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses. Journal of Cell Biology, 218(5), 1686-1705. https://doi.org/10.1083/jcb.201810023