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Article

Tubulin-Dependent Transport of Connexin-36 Potentiates the Size and Strength of Electrical Synapses

1
Department of Biology, York University, Toronto, ON M3J 1P3, Canada
2
Department of Biophysics and Physiology, Federal University of Rio de Janeiro-RJ, 21941-901 Rio de Janeiro, Brazil
3
Department of Neuroscience, Albert Einstein College, Bronx, NY 10461, USA
4
Department of Medicine, Albert Einstein College, Bronx, NY 10461, USA
5
Department of Psychology, York University, Toronto, ON M3J 1P3, Canada
*
Author to whom correspondence should be addressed.
Cells 2019, 8(10), 1146; https://doi.org/10.3390/cells8101146
Received: 30 August 2019 / Revised: 17 September 2019 / Accepted: 20 September 2019 / Published: 25 September 2019
(This article belongs to the Section Cell Signaling)
Connexin-36 (Cx36) electrical synapses strengthen transmission in a calcium/calmodulin (CaM)/calmodulin-dependent kinase II (CaMKII)-dependent manner similar to a mechanism whereby the N-methyl-D-aspartate (NMDA) receptor subunit NR2B facilitates chemical transmission. Since NR2B–microtubule interactions recruit receptors to the cell membrane during plasticity, we hypothesized an analogous modality for Cx36. We determined that Cx36 binding to tubulin at the carboxy-terminal domain was distinct from Cx43 and NR2B by binding a motif overlapping with the CaM and CaMKII binding motifs. Dual patch-clamp recordings demonstrated that pharmacological interference of the cytoskeleton and deleting the binding motif at the Cx36 carboxyl-terminal (CT) reversibly abolished Cx36 plasticity. Mechanistic details of trafficking to the gap-junction plaque (GJP) were probed pharmacologically and through mutational analysis, all of which affected GJP size and formation between cell pairs. Lys279, Ile280, and Lys281 positions were particularly critical. This study demonstrates that tubulin-dependent transport of Cx36 potentiates synaptic strength by delivering channels to GJPs, reinforcing the role of protein transport at chemical and electrical synapses to fine-tune communication between neurons. View Full-Text
Keywords: Connexin-36 (Cx36); gap junction; electrical plasticity; tubulin and microtubules; cytoskeleton; transport Connexin-36 (Cx36); gap junction; electrical plasticity; tubulin and microtubules; cytoskeleton; transport
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MDPI and ACS Style

Brown, C.A.; del Corsso, C.; Zoidl, C.; Donaldson, L.W.; Spray, D.C.; Zoidl, G. Tubulin-Dependent Transport of Connexin-36 Potentiates the Size and Strength of Electrical Synapses. Cells 2019, 8, 1146. https://doi.org/10.3390/cells8101146

AMA Style

Brown CA, del Corsso C, Zoidl C, Donaldson LW, Spray DC, Zoidl G. Tubulin-Dependent Transport of Connexin-36 Potentiates the Size and Strength of Electrical Synapses. Cells. 2019; 8(10):1146. https://doi.org/10.3390/cells8101146

Chicago/Turabian Style

Brown, Cherie A., Cristiane del Corsso, Christiane Zoidl, Logan W. Donaldson, David C. Spray, and Georg Zoidl. 2019. "Tubulin-Dependent Transport of Connexin-36 Potentiates the Size and Strength of Electrical Synapses" Cells 8, no. 10: 1146. https://doi.org/10.3390/cells8101146

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