TY - JOUR
T1 - Assembly of the postsynaptic membrane at the neuromuscular junction
T2 - Paradigm lost
AU - Kummer, Terrance T.
AU - Misgeld, Thomas
AU - Sanes, Joshua R.
N1 - Funding Information:
Research in our laboratories was supported by National Institutes of Health. T Misgeld was supported by an Emmy-Noether-Fellowship of the Deutsche Forschungsgemeinschaft. We thank J Lichtman for many crucial insights.
PY - 2006/2
Y1 - 2006/2
N2 - Studies of the vertebrate skeletal neuromuscular junction led to an influential model of how neurotransmitter receptors accumulate in the postsynaptic membrane. In this model, motor axons organize postsynaptic development by secreting neuregulin to induce acetylcholine receptor gene transcription in specialized subsynaptic nuclei, agrin to cluster diffuse receptors in the postsynaptic membrane, and acetylcholine to evoke electrical activity that promotes synaptic maturation. However, new studies in this area have first, demonstrated that axons sometimes innervate pre-existing receptor clusters; second, recast the roles of agrin and neuregulin; third, revealed early effects of neurotransmission; fourth, questioned the role of subsynaptic myonuclei; fifth, shown that elaborately-branched postsynaptic structures can form aneurally; and sixth, raised the possibility that neurotransmitter affects receptor type as well as distribution. These recent studies challenge the widely-held paradigms, although not the results that led to them, and suggest a new model for neuromuscular synaptogenesis.
AB - Studies of the vertebrate skeletal neuromuscular junction led to an influential model of how neurotransmitter receptors accumulate in the postsynaptic membrane. In this model, motor axons organize postsynaptic development by secreting neuregulin to induce acetylcholine receptor gene transcription in specialized subsynaptic nuclei, agrin to cluster diffuse receptors in the postsynaptic membrane, and acetylcholine to evoke electrical activity that promotes synaptic maturation. However, new studies in this area have first, demonstrated that axons sometimes innervate pre-existing receptor clusters; second, recast the roles of agrin and neuregulin; third, revealed early effects of neurotransmission; fourth, questioned the role of subsynaptic myonuclei; fifth, shown that elaborately-branched postsynaptic structures can form aneurally; and sixth, raised the possibility that neurotransmitter affects receptor type as well as distribution. These recent studies challenge the widely-held paradigms, although not the results that led to them, and suggest a new model for neuromuscular synaptogenesis.
UR - http://www.scopus.com/inward/record.url?scp=32344447256&partnerID=8YFLogxK
U2 - 10.1016/j.conb.2005.12.003
DO - 10.1016/j.conb.2005.12.003
M3 - Review article
C2 - 16386415
AN - SCOPUS:32344447256
SN - 0959-4388
VL - 16
SP - 74
EP - 82
JO - Current Opinion in Neurobiology
JF - Current Opinion in Neurobiology
IS - 1
ER -