Agrin and laminin induce acetylcholine receptor clustering by convergent, Rho GTPase-dependent signaling pathways

Abstract

Borges, L. S. and Ferns, M. (2001).

Skeletal Muscle IP3R1Receptors Amplify Physiological and Pathological Synaptic Calcium Signals

“…Although fetal AChRs are permeable to Ca 2+ , calpain remains activated well beyond the interval anticipated for AChR gating, suggesting that the Ca 2+ arises from another source (Chen et al, 2007). Because of the proximity of IP 3 R 1 to the mature NMJ, we tested whether persistent calpain activation required release of Ca 2+ through IP 3 Rs in C2C12 cells expressing laminin-induced AChR clusters (Weston et al, 2007). First, we applied the small interference RNA technique to selectively knock down IP 3 R 1 , the most abundant IP 3 R 1 in skeletal muscle (Wells, 2004).…”

“…Clearly numerous other neural factors, such as agrin and neuregulin, as well as sarcolemmal electrical activity, may also play roles in modulating gene expression and are likely to persist in intact NMJs after IP 3 R 1 silencing (Goldman et al, 1988; Lebrasseur et al, 2003; Weston et al, 2007). In some cases combined denervation and IP 3 R 1 silencing were similar or additive to single treatments, suggesting similar pathways, while in others, such as the greater effect of denervation on rapsyn and the opposing effect on AChE expression suggest that polypeptide neural factors may play a greater role in controlling expression of these genes.…”

Wnt signaling promotes AChR aggregation at the neuromuscular synapse in collaboration with agrin

“…Although Wnt3 can activate canonical signaling (3,(43)(44)(45)(46), in myotubes, Wnt3 regulates AChR clustering through a pathway that requires Rac1. Activation of Rac1 and RhoA correlates with the formation of micro-clusters and full-sized clusters, respectively (11,12,47). Compared with agrin, Wnt3 activates Rac1 more strongly than RhoA, and it induces the formation of only unstable AChR micro-clusters.…”

The RhoGAPcrossveinless-cInteracts withDystrophinand Is Required for Synaptic Homeostasis at theDrosophilaNeuromuscular Junction

“…Absence of dPix also compromises retrograde signaling, as reflected by reduced mEJPs and EJP amplitudes (Parnas et al, 2001). Similarly, the extracellular Dystroglycan-binding proteins Laminin and Agrin both signal through Rho GTPase-dependent pathways to initiate ACh receptor clustering (Weston et al, 2007). Finally, there is evidence for a RhoA-dependent postsynaptic role of ephexin-1 in regulation of clustering of acetylcholine neurotransmitter receptors at the murine NMJ (Shi et al, 2010).…”