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J Neurosci. 2014 Jun 18;34(25):8618-29. doi: 10.1523/JNEUROSCI.5081-13.2014.

Presynaptic clathrin levels are a limiting factor for synaptic transmission.

Author information

1
Laboratory of Neurobiology, Bellvitge Biomedical Research Institute (IDIBELL), and Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona, 08907 L'Hospitalet de Llobregat, Spain, and.
2
Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry CV4 7AL, United Kingdom allobet@ub.edu S.J.Royle@warwick.ac.uk.
3
Laboratory of Neurobiology, Bellvitge Biomedical Research Institute (IDIBELL), and Department of Pathology and Experimental Therapeutics, Faculty of Medicine, University of Barcelona, 08907 L'Hospitalet de Llobregat, Spain, and allobet@ub.edu S.J.Royle@warwick.ac.uk.

Abstract

To maintain communication, neurons must recycle their synaptic vesicles with high efficiency. This process places a huge burden on the clathrin-mediated endocytic machinery, but the consequences of this are poorly understood. We found that the amount of clathrin in a presynaptic terminal is not fixed. During stimulation, clathrin moves out of synapses as a function of stimulus strength and neurotransmitter release probability, which, together with membrane coat formation, transiently reduces the available pool of free clathrin triskelia. Correlative functional and morphological experiments in cholinergic autapses established by superior cervical ganglion neurons in culture show that presynaptic terminal function is compromised if clathrin levels fall by 20% after clathrin heavy chain knock down using RNAi. Synaptic transmission is depressed due to a reduction of cytoplasmic and readily releasable pools of vesicles. However, synaptic depression reverts after dialysis of exogenous clathrin, thus compensating RNAi-induced depletion. Lowering clathrin levels also reduces quantal size, which occurs concomitantly with a decrease in the size of synaptic vesicles. Large dense-core vesicles are unaffected by clathrin knock down. Together, our results show that clathrin levels are a dynamic property of presynaptic terminals that can influence short-term plasticity in a stimulus-dependent manner.

KEYWORDS:

clathrin; endocytosis; presynaptic; short-term depression; synaptic vesicle; synaptic vesicle pools

PMID:
24948816
DOI:
10.1523/JNEUROSCI.5081-13.2014
[Indexed for MEDLINE]
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