Version 1
: Received: 3 June 2024 / Approved: 4 June 2024 / Online: 4 June 2024 (14:12:24 CEST)
How to cite:
Jara, O.; Maripillán, J.; Momboisse, F.; Cárdenas, A. M.; García, I. E.; Martínez, A. D. Differential Regulation of Hemichannels and Gap Junction Channels by RhoA GTPase and Actin Cytoskeleton: A Comparative Analysis of Cx43 and Cx26. Preprints2024, 2024060200. https://doi.org/10.20944/preprints202406.0200.v1
Jara, O.; Maripillán, J.; Momboisse, F.; Cárdenas, A. M.; García, I. E.; Martínez, A. D. Differential Regulation of Hemichannels and Gap Junction Channels by RhoA GTPase and Actin Cytoskeleton: A Comparative Analysis of Cx43 and Cx26. Preprints 2024, 2024060200. https://doi.org/10.20944/preprints202406.0200.v1
Jara, O.; Maripillán, J.; Momboisse, F.; Cárdenas, A. M.; García, I. E.; Martínez, A. D. Differential Regulation of Hemichannels and Gap Junction Channels by RhoA GTPase and Actin Cytoskeleton: A Comparative Analysis of Cx43 and Cx26. Preprints2024, 2024060200. https://doi.org/10.20944/preprints202406.0200.v1
APA Style
Jara, O., Maripillán, J., Momboisse, F., Cárdenas, A. M., García, I. E., & Martínez, A. D. (2024). Differential Regulation of Hemichannels and Gap Junction Channels by RhoA GTPase and Actin Cytoskeleton: A Comparative Analysis of Cx43 and Cx26. Preprints. https://doi.org/10.20944/preprints202406.0200.v1
Chicago/Turabian Style
Jara, O., Isaac E. García and Agustín D. Martínez. 2024 "Differential Regulation of Hemichannels and Gap Junction Channels by RhoA GTPase and Actin Cytoskeleton: A Comparative Analysis of Cx43 and Cx26" Preprints. https://doi.org/10.20944/preprints202406.0200.v1
Abstract
Connexins (Cxs) are transmembrane proteins that assemble into gap junction channels (GJCs) and hemichannels (HCs). Previous research supports the involvement of Rho GTPases and actin microfilaments in the trafficking of Cxs, formation of GJCs plaques, and regulation of channel activity. Nonetheless, it remains uncertain whether distinct types of Cxs HCs and GJCs respond differently to Rho GTPases or changes in actin polymerization/depolymerization dynamics. Our investigation revealed that inhibiting RhoA, a small GTPase that controls actin polymerization, or disrupting actin microfilaments with cytochalasin B (Cyto-B), resulted in reduced GJCs plaque size at appositional membranes and increased transport of HCs to non-appositional plasma membrane regions. Notably, these effects were consistent across different Cx types, since Cx26 and Cx43 exhibited similar responses despite having distinct trafficking routes to the plasma membrane. Functional assessments showed that RhoA inhibition and actin depolymerization decreased the activity of Cx43 GJCs while significantly increasing HCs activity. However, the functional status of GJCs and HCs composed of Cx26 remained unaffected. This study supports the hypothesis that RhoA, through its control of the actin cytoskeleton, facilitates the transport of HCs to appositional cell membranes for GJCs formation while simultaneously limiting the positioning of free HCs at non-appositional cell membranes, independently of Cx type. This dynamic regulation promotes intercellular communication and reduces non-selective plasma membrane permeability through a Cx-type dependent mechanism, whereby Cx43 HCs and GJCs are affected, but Cx26 channels are not.
Keywords
connexin trafficking; cytochalasin-B; small GTPase; hemichannels; and gap junction channels regulation
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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