TY - JOUR
T1 - MACF1 links rapsyn to microtubule- and actin-binding proteins to maintain neuromuscular synapses
AU - Oury, Julien
AU - Liu, Yun
AU - Töpf, Ana
AU - Todorovic, Slobodanka
AU - Hoedt, Esthelle
AU - Preethish-Kumar, Veeramani
AU - Neubert, Thomas A.
AU - Lin, Weichun
AU - Lochmüller, Hanns
AU - Burden, Steven J.
N1 - Publisher Copyright:
© 2019 Oury et al.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
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U2 - 10.1083/jcb.201810023
DO - 10.1083/jcb.201810023
M3 - Article
C2 - 30842214
AN - SCOPUS:85065536054
SN - 0021-9525
VL - 218
SP - 1686
EP - 1705
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -