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Structural elements that underlie Doc2? function during asynchronous synaptic transmission.

ABSTRACT: Double C2-like domain-containing proteins alpha and beta (Doc2? and Doc2?) are tandem C2-domain proteins proposed to function as Ca(2+) sensors for asynchronous neurotransmitter release. Here, we systematically analyze each of the negatively charged residues that mediate binding of Ca(2+) to the ? isoform. The Ca(2+) ligands in the C2A domain were dispensable for Ca(2+)-dependent translocation to the plasma membrane, with one exception: neutralization of D220 resulted in constitutive translocation. In contrast, three of the five Ca(2+) ligands in the C2B domain are required for translocation. Importantly, translocation was correlated with the ability of the mutants to enhance asynchronous release when overexpressed in neurons. Finally, replacement of specific Ca(2+)/lipid-binding loops of synaptotagmin 1, a Ca(2+) sensor for synchronous release, with corresponding loops from Doc2?, resulted in chimeras that yielded slower kinetics in vitro and slower excitatory postsynaptic current decays in neurons. Together, these data reveal the key determinants of Doc2? that underlie its function during the slow phase of synaptic transmission.

SUBMITTER: Xue R

PROVIDER: S-EPMC4534243 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature

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Structural elements that underlie Doc2β function during asynchronous synaptic transmission.

Xue Renhao R Gaffaney Jon D JD Chapman Edwin R ER

Proceedings of the National Academy of Sciences of the United States of America 20150720 31

Double C2-like domain-containing proteins alpha and beta (Doc2α and Doc2β) are tandem C2-domain proteins proposed to function as Ca(2+) sensors for asynchronous neurotransmitter release. Here, we systematically analyze each of the negatively charged residues that mediate binding of Ca(2+) to the β isoform. The Ca(2+) ligands in the C2A domain were dispensable for Ca(2+)-dependent translocation to the plasma membrane, with one exception: neutralization of D220 resulted in constitutive translocati ...[more]

PMID: 26195798

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Dataset Information

Structural elements that underlie Doc2? function during asynchronous synaptic transmission.

Publications

Structural elements that underlie Doc2β function during asynchronous synaptic transmission.

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