期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 106, 期 43, 页码 18373-18378出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0910391106
关键词
acetylcholine receptor; endocytosis; neuromuscular junction; synapse formation
资金
- National Institutes of Health/National Institute of Neurological Disorders and Stroke
- International Human Frontier Science Program Organization
A critical step in synapse formation is the clustering of neurotransmitter receptors in the postsynaptic membrane, directly opposite the nerve terminal. At the neuromuscular junction, a widely studied model synapse, acetylcholine receptors (AChRs) initially aggregate to form an ovoid postsynaptic plaque. As the synapse matures, the plaque becomes perforated and is eventually transformed into a complex, branched structure. We found that this transformation also occurs in myotubes cultured in the absence of neurons, and used this system to seek machinery that orchestrates postsynaptic maturation. We show that perforations in the AChR aggregate bear structures resembling podosomes, dynamic actin-rich adhesive organelles involved in matrix remodeling in non-neuronal cells but not described in neural structures. The location and dynamics of synaptic podosomes are spatiotemporally correlated with changes in AChR aggregate topology, and pharmacological disruption of podosomes leads to rapid alterations in AChR organization. Our results indicate that synaptic podosomes play critical roles in maturation of the postsynaptic membrane.
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