Agrin regulates acetylcholine receptors at the neuromuscular junction by locally stabilizing microtubules through the plus end tracking proteins CLASP2 and CLIP-170.

A novel mechanism is described for the agrin-mediated focal delivery of acetylcholine receptors (AChRs) to the postsynaptic membrane of the neuromuscular junction. Microtubule capture mediated by CLASP2 and its interaction partner, LL5β, and an intact subsynaptic actin cytoskeleton are both required for focal AChR transport to the synaptic membrane.

Although the role of Wnt signalling in breast cancer is far from being fully understood, in the last years its importance has been reported frequently. Besides stimulation by canonical Wnt signalling, the downstream effectors β-catenin and the transcriptional modulators of the T-cell factor/lymphoid enhancer-binding factor (TCF/LEF) family can also be activated by other inputs including the TGF-β pathway. Wnt and TGF-β signalling are both major signal transduction pathways, which provide important cues during development and tumor progression. However, particularly TGF-β has a complicated influence on oncogenesis, which ranges from suppressive to promoting activity. Signalling pathways activated in parallel with TGF-β might determine the oncogenic influence, and therefore place signals cooperating with TGF-β into the limelight. During early development Wnt and TGF-β signalling collaborate extensively. Here we provide an overview of the known interactions of Wnt with TGF-β signalling in development and metastasis, particularly in breast cancer. We want to focus on the Wnt-activated transcription factor complex β-catenin/LEF-1, its upstream activators, its downstream targets and consequences on the cellular level in response to β-catenin/LEF-1 activation.

Background:The plus-end-binding protein CLASP2 was shown to regulate MT capture at the neuromuscular junction. Results: GSK3␤-mediated CLASP2 phosphorylation regulates CLASP2-MT binding and AChR insertion at synaptic clusters. Conclusion:The agrin-induced control of CLASP2 phosphorylation is an important mechanism for MT capture and synaptic AChR clustering. Significance: Agrin-induced AChR delivery to synaptic AChR clusters through CLASP2-mediated MT capture ensures efficient clustering of AChRs at the synaptic muscle membrane.

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