The synaptic muscle‐specific kinase (MuSK) complex: New partners, new functions

Strochlic, Laure; Cartaud, Annie; Cartaud, Jean

doi:10.1002/bies.20305

Cited by 63 publications

(51 citation statements)

References 64 publications

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“…This nerve-independent patterning of AChR expression, termed muscle prepatterning, is dependent upon MuSK (Lin et al, 2001;Yang et al, 2001), a receptor tyrosine kinase that is activated by Agrin and essential for neuromuscular synapse formation (DeChiara et al, 1996;Strochlic et al, 2005). To determine whether MuSK itself is prepatterned in muscle lacking motor axons, we examined the pattern of MuSK expression in muscles from mice that lack motor axons.…”

Section: Musk Expression Is Patterned In Muscle Lacking Motor Axonsmentioning

confidence: 99%

MuSK controls where motor axons grow and form synapses

2007

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SummaryIt had long been thought that motor axons approach muscles that are regionally unspecialized and induce postsynaptic differentiation by releasing signals that focally initiate transcriptional and post-translational responses in muscle. This neuro-centric view of synapse formation, however, has been challenged by recent experiments, which showed that AChR clusters are concentrated in the central region of muscle independent of innervation. This nerve-independent prepattern of AChR expression requires MuSK, a receptor tyrosine kinase that is critical for synapse formation. How muscle prepatterning is established and whether motor axons recognize this prepattern are not known. Here, we show that MuSK itself is prepatterned in muscle and that high, ectopic MuSK expression is sufficient to promote ectopic motor axon growth and synapse formation, indicating that the muscle prepattern is recognized by motor axons and promotes synapse formation in the central region of developing mammalian muscle. Further, we provide evidence that early expression of MuSK in developing myotubes is sufficient to re-establish muscle prepatterning independent of the MuSK promoter. Moreover, we show that ectopic MuSK expression stimulates synapse formation in the absence of Agrin and rescues the neonatal lethality of agrin mutant mice, demonstrating that MuSK, independent of Agrin, is sufficient to direct presynaptic and postsynaptic differentiation. In contrast to a neuro-centric view for synapse formation, these data demonstrate that the postsynaptic cell can play a dominant role in regulating synapse formation.

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Section: Musk Expression Is Patterned In Muscle Lacking Motor Axonsmentioning

confidence: 99%

MuSK controls where motor axons grow and form synapses

2007

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“…[49][50] Three different kinships have been described so far in association with Musk deficiency. 11-51-52 Despite significant variability in clinical phenotype and disease severity, most patients had ocular symptoms and fatigable limb weakness.…”

Section: Musk Deficiencymentioning

confidence: 99%

Genetic heterogeneity and pathophysiological mechanisms in congenital myasthenic syndromes

Barišić

Chaouch

Müller

et al. 2011

European Journal of Paediatric Neurology

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“…Although this similarity suggests that MuSK might modulate hippocampal nicotinic transmission through effects on receptor clustering, it is notable that MuSK plays a pleiotropic role in signaling. For example, activated MuSK recruits phosphotyrosine-binding proteins to regulate transcription via the Ras and Rac/CDC42 pathways (Strochlic et al, 2005). Moreover, the cytoplasmic PDZ [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] domain of MuSK suggests the possibility of a direct interaction with PSD-95, a scaffolding protein that is critical for the organization and function of the glutamatergic synapses whose activation generates theta activity (ElHusseini et al, 2000;Schnell et al, 2002).…”

Section: The Role Of Musk In Oscillatory Behavior and Synaptic Plastimentioning

confidence: 99%

MuSK Expressed in the Brain Mediates Cholinergic Responses, Synaptic Plasticity, and Memory Formation

et al. 2006

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Muscle-specific tyrosine kinase receptor (MuSK) has been believed to be mainly expressed and functional in muscle, in which it mediates the formation of neuromuscular junctions. Here we show that MuSK is expressed in the brain, particularly in neurons, as well as in non-neuronal tissues. We also provide evidence that MuSK expression in the hippocampus is required for memory consolidation, because temporally restricted knockdown after training impairs memory retention. Hippocampal disruption of MuSK also prevents the learning-dependent induction of both cAMP response element binding protein (CREB) phosphorylation and CCAAT enhancer binding protein ␤ (C/EBP␤) expression, suggesting that the role of MuSK during memory consolidation critically involves the CREB-C/EBP pathway. Furthermore, we found that MuSK also plays an important role in mediating hippocampal oscillatory activity in the theta frequency as well as in the induction and maintenance of long-term potentiation, two synaptic responses that correlate with memory formation. We conclude that MuSK plays an important role in brain functions, including memory formation. Therefore, its expression and role are broader than what was believed previously.

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The synaptic muscle‐specific kinase (MuSK) complex: New partners, new functions

Cited by 63 publications

References 64 publications

MuSK controls where motor axons grow and form synapses

MuSK controls where motor axons grow and form synapses

Genetic heterogeneity and pathophysiological mechanisms in congenital myasthenic syndromes

MuSK Expressed in the Brain Mediates Cholinergic Responses, Synaptic Plasticity, and Memory Formation

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