The Cx43-like Connexin Protein Cx40.8 is Differentially Localized During Fin Ontogeny and Fin Regeneration

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Feb 21

PMID 22347467

Citations 10

Authors

Sarah V Gerhart

Diane M Eble

R Michael Burger

Stefan N Oline

Ana Vacaru

Kirsten C Sadler

Rebecca Jefferis

M Kathryn Iovine

Affiliations

Soon will be listed here.

Abstract

Connexins (Cx) are the subunits of gap junctions, membraneous protein channels that permit the exchange of small molecules between adjacent cells. Cx43 is required for cell proliferation in the zebrafish caudal fin. Previously, we found that a Cx43-like connexin, cx40.8, is co-expressed with cx43 in the population of proliferating cells during fin regeneration. Here we demonstrate that Cx40.8 exhibits novel differential subcellular localization in vivo, depending on the growth status of the fin. During fin ontogeny, Cx40.8 is found at the plasma membrane, but Cx40.8 is retained in the Golgi apparatus during regeneration. We next identified a 30 amino acid domain of Cx40.8 responsible for its dynamic localization. One possible explanation for the differential localization is that Cx40.8 contributes to the regulation of Cx43 in vivo, perhaps modifying channel activity during ontogenetic growth. However, we find that the voltage-gating properties of Cx40.8 are similar to Cx43. Together our findings reveal that Cx40.8 exhibits differential subcellular localization in vivo, dependent on a discrete domain in its carboxy terminus. We suggest that the dynamic localization of Cx40.8 differentially influences Cx43-dependent cell proliferation during ontogeny and regeneration.

Citing Articles

Osteocyte connexin hemichannels and prostaglandin E release dictate bone marrow mesenchymal stromal cell commitment.

Zhang J, Acosta F, Wang X, Zhao D, Zhang L, Hua R Proc Natl Acad Sci U S A. 2025; 122(7):e2412144122.

PMID: 39937859 PMC: 11848350. DOI: 10.1073/pnas.2412144122.

Atrial natriuretic peptide signaling co-regulates lipid metabolism and ventricular conduction system gene expression in the embryonic heart.

Mishra A, Tavasoli M, Sokolenko S, McMaster C, Pasumarthi K iScience. 2024; 27(1):108748.

PMID: 38235330 PMC: 10792247. DOI: 10.1016/j.isci.2023.108748.

Role of the Connexin C-terminus in skin pattern formation of Zebrafish.

Usui Y, Watanabe M BBA Adv. 2023; 1:100006.

PMID: 37082017 PMC: 10074918. DOI: 10.1016/j.bbadva.2021.100006.

Transgenic fluorescent zebrafish lines that have revolutionized biomedical research.

Choe C, Choi S, Kee Y, Kim M, Kim S, Lee Y Lab Anim Res. 2021; 37(1):26.

PMID: 34496973 PMC: 8424172. DOI: 10.1186/s42826-021-00103-2.

Impaired Cx43 gap junction endocytosis causes morphological and functional defects in zebrafish.

Hyland C, Mfarej M, Hiotis G, Lancaster S, Novak N, Iovine M Mol Biol Cell. 2021; 32(20):ar13.

PMID: 34379446 PMC: 8684743. DOI: 10.1091/mbc.E20-12-0797.

References

Martin , Steggles , Wilson , Ahmad , Evans . Targeting motifs and functional parameters governing the assembly of connexins into gap junctions. Biochem J. 2000; 350 Pt 3:943. PMC: 1221330. View

Lippincott-Schwartz J, Yuan L, Bonifacino J, Klausner R . Rapid redistribution of Golgi proteins into the ER in cells treated with brefeldin A: evidence for membrane cycling from Golgi to ER. Cell. 1989; 56(5):801-13. PMC: 7173269. DOI: 10.1016/0092-8674(89)90685-5. View

Iovine M, Johnson S . Genetic analysis of isometric growth control mechanisms in the zebrafish caudal Fin. Genetics. 2000; 155(3):1321-9. PMC: 1461173. DOI: 10.1093/genetics/155.3.1321. View

Lauf U, Lopez P, Falk M . Expression of fluorescently tagged connexins: a novel approach to rescue function of oligomeric DsRed-tagged proteins. FEBS Lett. 2001; 498(1):11-5. DOI: 10.1016/s0014-5793(01)02462-0. View

Fiorini C, Decrouy X, Defamie N, Segretain D, Pointis G . Opposite regulation of connexin33 and connexin43 by LPS and IL-1alpha in spermatogenesis. Am J Physiol Cell Physiol. 2005; 290(3):C733-40. DOI: 10.1152/ajpcell.00106.2005. View

Ahmad S, Martin P, Evans W . Assembly of gap junction channels: mechanism, effects of calmodulin antagonists and identification of connexin oligomerization determinants. Eur J Biochem. 2001; 268(16):4544-52. DOI: 10.1046/j.1432-1327.2001.02380.x. View

Elfgang C, Eckert R, Lichtenberg-Frate H, Butterweck A, Traub O, Klein R . Specific permeability and selective formation of gap junction channels in connexin-transfected HeLa cells. J Cell Biol. 1995; 129(3):805-17. PMC: 2120441. DOI: 10.1083/jcb.129.3.805. View

Gerido D, White T . Connexin disorders of the ear, skin, and lens. Biochim Biophys Acta. 2004; 1662(1-2):159-70. DOI: 10.1016/j.bbamem.2003.10.017. View

Iovine M, Higgins E, Hindes A, Coblitz B, Johnson S . Mutations in connexin43 (GJA1) perturb bone growth in zebrafish fins. Dev Biol. 2005; 278(1):208-19. DOI: 10.1016/j.ydbio.2004.11.005. View

10.

Giepmans B, Verlaan I, Hengeveld T, Janssen H, Calafat J, Falk M . Gap junction protein connexin-43 interacts directly with microtubules. Curr Biol. 2001; 11(17):1364-8. DOI: 10.1016/s0960-9822(01)00424-9. View

11.

Sims Jr K, Eble D, Iovine M . Connexin43 regulates joint location in zebrafish fins. Dev Biol. 2009; 327(2):410-8. PMC: 2913275. DOI: 10.1016/j.ydbio.2008.12.027. View

12.

Goldberg G, Valiunas V, Brink P . Selective permeability of gap junction channels. Biochim Biophys Acta. 2004; 1662(1-2):96-101. DOI: 10.1016/j.bbamem.2003.11.022. View

13.

Cottrell G, Burt J . Functional consequences of heterogeneous gap junction channel formation and its influence in health and disease. Biochim Biophys Acta. 2005; 1711(2):126-41. DOI: 10.1016/j.bbamem.2004.11.013. View

14.

Hoptak-Solga A, Nielsen S, Jain I, Thummel R, Hyde D, Iovine M . Connexin43 (GJA1) is required in the population of dividing cells during fin regeneration. Dev Biol. 2008; 317(2):541-8. PMC: 2429987. DOI: 10.1016/j.ydbio.2008.02.051. View

15.

Sohl G, Willecke K . Gap junctions and the connexin protein family. Cardiovasc Res. 2004; 62(2):228-32. DOI: 10.1016/j.cardiores.2003.11.013. View

16.

Paznekas W, Boyadjiev S, Shapiro R, Daniels O, Wollnik B, Keegan C . Connexin 43 (GJA1) mutations cause the pleiotropic phenotype of oculodentodigital dysplasia. Am J Hum Genet. 2002; 72(2):408-18. PMC: 379233. DOI: 10.1086/346090. View

17.

Gilleron J, Fiorini C, Carette D, Avondet C, Falk M, Segretain D . Molecular reorganization of Cx43, Zo-1 and Src complexes during the endocytosis of gap junction plaques in response to a non-genomic carcinogen. J Cell Sci. 2008; 121(Pt 24):4069-78. DOI: 10.1242/jcs.033373. View

18.

Brink P, Cronin K, Banach K, Peterson E, Westphale E, Seul K . Evidence for heteromeric gap junction channels formed from rat connexin43 and human connexin37. Am J Physiol. 1997; 273(4):C1386-96. DOI: 10.1152/ajpcell.1997.273.4.C1386. View

19.

Carette D, Gilleron J, Decrouy X, Fiorini C, Diry M, Segretain D . Connexin 33 impairs gap junction functionality by accelerating connexin 43 gap junction plaque endocytosis. Traffic. 2009; 10(9):1272-85. DOI: 10.1111/j.1600-0854.2009.00949.x. View

20.

Gerhart S, Jefferis R, Iovine M . Cx40.8, a Cx43-like protein, forms gap junction channels inefficiently and may require Cx43 for its association at the plasma membrane. FEBS Lett. 2009; 583(21):3419-24. PMC: 2785097. DOI: 10.1016/j.febslet.2009.09.054. View