Emerging roles for MAP kinases in agrin signaling.

Information between neurons and the target cells they innervate passes through sites of functional contact called synapses. How synapses form and are altered by sensory or cognitive experience is central to understand nervous system function. Studies of synapse formation and plasticity have concentrated on a few "model" synapses. The vertebrate neuromuscular junction (NMJ), the synapse between a motoneuron in the spinal cord and a skeletal muscle fiber, is one such model synapse. The extracellular matrix proteoglycan agrin plays an essential organizing role at the NMJ. Agrin is also present at some synapses in the brain and in other organs in the periphery, but its function outside the NMJ is unclear. The core signaling pathway for agrin at the NMJ, which is still incompletely defined, includes molecules specifically involved in this cascade and molecules used in other signaling pathways in many cells. Mitogen-activated protein kinases (MAPKs) are evolutionarily conserved components of intracellular signaling modules that control a myriad of cellular processes. This article reviews emerging evidence that suggests that MAPKs are involved in agrin signaling at the NMJ and in the putative functions of agrin in the formation of a subset of synapses in the brain.