Doc2 Supports Spontaneous Synaptic Transmission by a Ca2+-Independent Mechanism

Zhiping P. Pang, Taulant Bacaj, Xiaofei Yang, Peng Zhou, Wei Xu, Thomas C. Südhof

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

Two families of Ca2+-binding proteins have been proposed as Ca2+ sensors for spontaneous release: synaptotagmins and Doc2s, with the intriguing possibility that Doc2s may represent high-affinity Ca2+ sensors that are activated by deletion of synaptotagmins, thereby accounting for the increased spontaneous release in synaptotagmin-deficient synapses. Here, we use an shRNA-dependent quadruple knockdown of all four Ca2+-binding proteins of the Doc2 family to confirm that Doc2-deficient synapses exhibit a marked decrease in the frequency of spontaneous release events. Knockdown of Doc2s in synaptotagmin-1-deficient synapses, however, failed to reduce either the increased spontaneous release or the decreased evoked release of these synapses, suggesting that Doc2s do not constitute Ca2+ sensors for asynchronous release. Moreover, rescue experiments revealed that the decrease in spontaneous release induced by the Doc2 knockdown in wild-type synapses is fully reversed by mutant Doc2B lacking Ca2+-binding sites. Thus, our data suggest that Doc2s are modulators of spontaneous synaptic transmission that act by a Ca2+-independent mechanism.

Original languageEnglish (US)
Pages (from-to)244-251
Number of pages8
JournalNeuron
Volume70
Issue number2
DOIs
StatePublished - Apr 28 2011

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Synaptic Transmission
Synapses
Synaptotagmins
Carrier Proteins
Synaptotagmin I
Small Interfering RNA
Binding Sites

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Doc2 Supports Spontaneous Synaptic Transmission by a Ca2+-Independent Mechanism. / Pang, Zhiping P.; Bacaj, Taulant; Yang, Xiaofei; Zhou, Peng; Xu, Wei; Südhof, Thomas C.

In: Neuron, Vol. 70, No. 2, 28.04.2011, p. 244-251.

Research output: Contribution to journalArticle

Pang, ZP, Bacaj, T, Yang, X, Zhou, P, Xu, W & Südhof, TC 2011, 'Doc2 Supports Spontaneous Synaptic Transmission by a Ca2+-Independent Mechanism', Neuron, vol. 70, no. 2, pp. 244-251. https://doi.org/10.1016/j.neuron.2011.03.011
Pang, Zhiping P. ; Bacaj, Taulant ; Yang, Xiaofei ; Zhou, Peng ; Xu, Wei ; Südhof, Thomas C. / Doc2 Supports Spontaneous Synaptic Transmission by a Ca2+-Independent Mechanism. In: Neuron. 2011 ; Vol. 70, No. 2. pp. 244-251.
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