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Wiring the Brain: Agrin-MuSK Pathway

NEURO-VTPW1M

The protein agrin is a principal component of a signaling pathway that underlies the formation of the neuromuscular junction (NMJ), which is the synaptic connections between motor neurons and muscle fibers.

Agrin is released by the pre-synaptic terminal and binds to Lrp4 receptors on the muscle fiber. Signal transduction from Lrp4 receptors involves activation and tyrosine phosphorylation of the receptor tyrosine kinase MuSK that directly associates with Lrp4.

Next, MuSK phosphorylates and recruits the adaptor protein Dok-7. Activation of Dok-7 ultimately results in the phosphorylation and clustering of acetylcholine receptors (AChR) on the post-synaptic membrane.

Stanislav Kholmanskikh. Created for Albert.io. Copyright 2016. All rights reserved.

From the statements below, select only those that confirm the role of the Agrin-MuSK signaling pathway in synaptic differentiation as described above.

Select ALL that apply.

A

Pre-patterning of the muscle fibers, where AChR are concentrated in their central regions prior to innervation, is abolished in the absence of MuSK or Lrp4.

B

Pre-patterning of the muscle fibers, where AChR are concentrated in their central regions prior to innervation, is intact in the absence of Agrin. However, nascent clustering of AChR cannot be stabilized upon innervation and NMJ never forms.

C

Neonatal (newborn) mice that lack Agrin, Lrp4, MuSK or Dok-7 have identical phenotypes that include the absence of the NMJ, failure to breathe, and death at birth.

D

Acetylcholine released by the axonal terminal is responsible for the dispersion of the AChR. This ensures that AChR only clusters at synaptic sites.