Complexin II plays a positive role in Ca
            <sup>2+</sup>
            -triggered exocytosis by facilitating vesicle priming

Cai, Haijiang; Reim, Kerstin; Varoqueaux, Frédérique; Tapechum, Sompol; Hill, Kerstin; Sørensen, Jakob B.; Chow, Robert H.

doi:10.1073/pnas.0810232105

Cited by 67 publications

(85 citation statements)

References 46 publications

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“…No major change in the kinetics of sucrose-induced EPSCs was observed. The decrease in the RRP induced by the Cpx1/2 DKD and DKO is consistent with previous results suggesting that complexins are essential for synaptic vesicle priming (15,17,28,31). All DKO phenotypes were rescued in cortical neurons by wild-type Cpx1, demonstrating that they are produced by the complexin deletion (Fig.…”

Section: Resultssupporting

confidence: 79%

“…Increasing numbers of studies indicate that complexin performs a fundamental general function in Ca 2+ -stimulated exocytosis that is not limited to the synapse. For example, complexin is involved in chromaffin granule exocytosis, which resembles the exocytosis of large dense-core vesicles (31), and is essential for Ca 2+ -induced exocytosis of IGF1-containing secretory vesicles in mitral neurons that depends on a different synaptotagmin isoform (Syt10) than synaptic and neuroendocrine exocytosis (Syt1, Syt2, Syt7, and Syt9) (32). A major cause for the uncertainty of complexin function at least in mammalian neurons is that the phenotypes of the DKO and DKD neurons have not been directly compared in the same electrophysiological preparation.…”

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confidence: 99%

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Deconstructing complexin function in activating and clamping Ca ²⁺ -triggered exocytosis by comparing knockout and knockdown phenotypes

Yang

Cao

Südhof

2013

Proc. Natl. Acad. Sci. U.S.A.

103

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Complexin, a presynaptic protein that avidly binds to assembled SNARE complexes, is widely acknowledged to activate Ca 2+ -triggered exocytosis. In addition, studies of invertebrate complexin mutants and of mouse neurons with a double knockdown (DKD) of complexin-1 and -2 suggested that complexin maintains the readily releasable pool (RRP) of vesicles and clamps spontaneous exocytosis. In contrast, studies of mouse neurons with a double knockout (DKO) of complexin-1 and -2, largely carried out in hippocampal autapses, did not detect changes in the RRP size or in spontaneous exocytosis. To clarify complexin function, we here directly compared in two different preparations, cultured cortical and olfactory bulb neurons, the phenotypes of complexin DKD and DKO neurons. We find that complexin-deficient DKD and DKO neurons invariably exhibit a ∼50% decrease in vesicle priming. Moreover, the DKD consistently increased spontaneous exocytosis, but the DKO did so in cortical but not olfactory bulb neurons. Furthermore, the complexin DKD but not the complexin DKO caused a compensatory increase in complexin-3 and -4 mRNA levels; overexpression of complexin-3 but not complexin-1 increased spontaneous exocytosis. Complexin-3 but not complexin-1 contains a C-terminal lipid anchor attaching it to the plasma membrane; addition of a similar lipid anchor to complexin-1 converted complexin-1 from a clamp into an activator of spontaneous exocytosis. Viewed together, our data suggest that complexin generally functions in priming and Ca 2+ triggering of exocytosis, and additionally contributes to the control of spontaneous exocytosis dependent on the developmental history of a neuron and on the subcellular localization of the complexin. synaptic transmission | neurotransmitter release | synaptotagmin | SNARE protein | membrane fusion

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Section: Resultssupporting

confidence: 79%

mentioning

confidence: 99%

Deconstructing complexin function in activating and clamping Ca ²⁺ -triggered exocytosis by comparing knockout and knockdown phenotypes

Yang

Cao

Südhof

2013

Proc. Natl. Acad. Sci. U.S.A.

103

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“…A candidate molecule to regulate the balance between the HCSP and the RRP is complexin. Such a role is supported by recent findings (54)(55)(56), which suggest that complexin stabilizes full SNARE complex formation, preventing nontriggered fusion by raising the concentration of calcium required for release and reducing the rate of back transition to the HCSP. This would have the effect of reducing release in the short run but of increasing potential release in response to a large increase of Ca 2ϩ influx.…”

Section: Discussionsupporting

confidence: 65%

Newcomer insulin secretory granules as a highly calcium-sensitive pool

Pedersen

Sherman

2009

Proc. Natl. Acad. Sci. U.S.A.

118

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Insulin secretion is biphasic in response to a step in glucose stimulation. Recent experiments suggest that 2 different mechanisms operate during the 2 phases, with transient first-phase secretion due to exocytosis of docked granules but the second sustained phase due largely to newcomer granules. Another line of research has shown that there exist 2 pools of releasable granules with different Ca 2؉ sensitivities. An immediately releasable pool (IRP) is located in the vicinity of Ca 2؉ channels, whereas a highly Ca 2؉ -sensitive pool (HCSP) resides mainly away from Ca 2؉ channels. We extend a previous model of exocytosis and insulin release by adding an HCSP and show that the inclusion of this pool naturally leads to insulin secretion mainly from newcomer granules during the second phase of secretion. We show that the model is compatible with data from single cells on the HCSP and from stimulation of islets by glucose, including L-and R-type Ca 2؉ channel knockouts, as well as from Syntaxin-1A-deficient cells. We also use the model to investigate the relative contribution of calcium signaling and pool depletion in controlling biphasic secretion.␤-cells ͉ biphasic secretion ͉ exocytosis ͉ pancreatic islets ͉ vesicles

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“…Their deletion in mice causes profound deficits in release probability, evoked transmitter release and reduced spontaneous release at neuronal synapses (Reim et al, 2001;Xue et al, 2007;Xue et al, 2008), as well as reduced secretory granule fusion in adrenal chromaffin cells (Cai et al, 2008), which indicates that complexins act as positive regulators at or following the Ca 2+ -triggering step of synaptic vesicle fusion. The notion that complexins act as facilitators of SNARE-mediated secretory vesicle fusion is also supported by the observation that overexpression of Cplx2 in wild-type chromaffin cells increases chromaffin granule secretion (Cai et al, 2008).…”

Section: +mentioning

confidence: 99%

Aberrant function and structure of retinal ribbon synapses in the absence of complexin 3 and complexin 4

Reim

Regus-Leidig

Ammermüller

et al. 2009

Journal of Cell Science

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Complexins regulate the speed and Ca2+ sensitivity of SNARE-mediated synaptic vesicle fusion at conventional synapses. Two of the vertebrate complexins, Cplx3 and Cplx4, are specifically localized to retinal ribbon synapses. To test whether Cplx3 and Cplx4 contribute to the highly efficient transmitter release at ribbon synapses, we studied retina function and structure in Cplx3 and Cplx4 single- and double-knockout mice. Electroretinographic recordings from single and double mutants revealed a cooperative perturbing effect of Cplx3 and Cplx4 deletion on the b-wave amplitude, whereas most other detected effects in both plexiform synaptic layers were additive. Light and electron microscopic analyses uncovered a disorganized outer plexiform layer in the retinae of mice lacking Cplx3 and Cplx4, with a significant proportion of photoreceptor terminals containing spherical free-floating ribbons. These structural and functional aberrations were accompanied by behavioural deficits indicative of a vision deficit. Our results show that Cplx3 and Cplx4 are essential regulators of transmitter release at retinal ribbon synapses. Their loss leads to aberrant adjustment and fine-tuning of transmitter release at the photoreceptor ribbon synapse, alterations in transmission at bipolar cell terminals, changes in the temporal structure of synaptic processing in the inner plexiform layer of the retina and perturbed vision.

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Complexin II plays a positive role in Ca ²⁺ -triggered exocytosis by facilitating vesicle priming

Abstract: chromaffin cell ͉ large dense core vesicle ͉ SNARE complex

Cited by 67 publications

References 46 publications

Deconstructing complexin function in activating and clamping Ca ²⁺ -triggered exocytosis by comparing knockout and knockdown phenotypes

Deconstructing complexin function in activating and clamping Ca ²⁺ -triggered exocytosis by comparing knockout and knockdown phenotypes

Newcomer insulin secretory granules as a highly calcium-sensitive pool

Aberrant function and structure of retinal ribbon synapses in the absence of complexin 3 and complexin 4

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Complexin II plays a positive role in Ca 2+ -triggered exocytosis by facilitating vesicle priming

Abstract: chromaffin cell ͉ large dense core vesicle ͉ SNARE complex

Cited by 67 publications

References 46 publications

Deconstructing complexin function in activating and clamping Ca 2+ -triggered exocytosis by comparing knockout and knockdown phenotypes

Deconstructing complexin function in activating and clamping Ca 2+ -triggered exocytosis by comparing knockout and knockdown phenotypes

Newcomer insulin secretory granules as a highly calcium-sensitive pool

Aberrant function and structure of retinal ribbon synapses in the absence of complexin 3 and complexin 4

Contact Info

Product

Resources

About

Complexin II plays a positive role in Ca ²⁺ -triggered exocytosis by facilitating vesicle priming

Deconstructing complexin function in activating and clamping Ca ²⁺ -triggered exocytosis by comparing knockout and knockdown phenotypes

Deconstructing complexin function in activating and clamping Ca ²⁺ -triggered exocytosis by comparing knockout and knockdown phenotypes