期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 6, 页码 2175-2180出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0712171105
关键词
clathrin; electron microscopy; endocytosis; synapse; synaptojanin
资金
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
- NCI NIH HHS [CA46128, P01 CA046128] Funding Source: Medline
- NCRR NIH HHS [P41 RR000592, RR-000592] Funding Source: Medline
- NIDA NIH HHS [DA018343, P30 DA018343] Funding Source: Medline
- NIDDK NIH HHS [P30 DK045735, DK45735] Funding Source: Medline
- NINDS NIH HHS [R37 NS036251, NS36251, R01 NS036251] Funding Source: Medline
- Telethon [GGP05141] Funding Source: Medline
Mice lacking expression of dynamin 1, a GTPase implicated in the fission reaction of synaptic vesicle endocytosis, fail to thrive and exhibit severe activity-dependent endocytic defects at their synapses. Here, we have used electron tomography to investigate the massive increase in clathrin-coated pit abundance that is selectively observed at a subset of synapses in dynamin 1 KO primary neuron cultures under conditions of spontaneous network activity. This increase, leading to branched tubular plasma membrane invaginations capped by clathrin-coated buds, occurs selectively at inhibitory synapses. A similar massive increase of clathrin-coated profiles (in this case, of clathrin-coated vesicles) is observed at inhibitory synapses of neurons that lack expression of synaptojanin 1, a phosphoinositide phosphatase involved in clathrin-coated vesicle uncoating. Thus, although excitatory synapses are largely spared under these conditions, inhibitory synapses are uniquely sensitive to perturbation of endocytic proteins, probably as a result of their higher levels of tonic activity leading to a buildup of clathrin-coated intermediates in these synapses. In contrast, the predominant endocytic structures observed at the majority of dynamin 1 KO synapses after acute stimulation are endosome-like intermediates that originate by a dynamin 1-independent form of endocytosis. These findings reveal a striking heterogeneity in the mode of synaptic vesicle recycling in different synapses and functional states.
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