Editors' ChoiceNEUROMUSCULAR JUNCTION

Agrin Recruits APC

Science's STKE  14 Oct 2003:
Vol. 2003, Issue 204, pp. tw408-TW408
DOI: 10.1126/stke.2003.204.tw408

Agrin is a secreted, motor neuron-derived heparan sulfate proteoglycan that is required for the development of the postsynaptic region of the neuromuscular junction. After activating its receptor, the muscle-specific kinase, acetylcholine receptors (AChRs) on the surface of muscle fibers aggregate into high-density clusters and become anchored to the cytoskeleton. Wang et al. determined that the cytoplasmic domain of the AChR β subunit interacted with the tumor suppressor protein adenomatous polyposis coli (APC) in response to agrin. Treatment of cultured myotubes with agrin stimulated relocalization of APC from the cytoplasm and nucleus to clustered AChRs. Expression of a competing fragment of APC blocked formation of AChR clusters in response to agrin. APC interacts with actin and microtubules, and the authors propose that the observed APC β subunit association may link AChRs to the cytoskeleton and facilitate specification of the neuromuscular junction. The interaction also suggests possible cross-talk between the agrin pathway and Wnt/β-catenin-APC pathway.

J. Wang, Z. Jing, L. Zhang, G. Zhou, J. Braun, Y. Yao, Z.-Z. Wang, Regulation of acetylcholine receptor clustering by the tumor suppressor APC. Nat. Neurosci. 6, 1017-1018 (2003). [Online Journal]