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.
Highlights
Connexins, the subunits of gap junction channels, are part of a large multigene family that includes about 20 genes in mammals [1]
Most tissues express a unique complement of 2–7 connexin genes, suggesting that distinct homomeric and heteromeric gap junction channels contribute to cell-cell coupling and functional diversity
Cx40.8 co-assembles with Cx43 in gap junction channels We previously found that Cx40.8 is capable of co-localizing to gap junction plaques in HeLa cells when co-transfected with Cx43 [17], suggesting that Cx43 and Cx40.8 could associate in common gap junction channels
Summary
The subunits of gap junction channels, are part of a large multigene family that includes about 20 genes in mammals [1]. Six connexin proteins oligomerize to form one connexon (or hemichannel), and the docking of two connexons at the plasma membranes of neighboring cells forms a single gap junction channel. Channels associate together at the plasma membrane to form gap junction plaques, permitting the passage of ions and small molecules (,1200 Da) between adjacent cells. Most tissues express a unique complement of 2–7 connexin genes, suggesting that distinct homomeric and heteromeric gap junction channels contribute to cell-cell coupling and functional diversity (reviewed in [2]). One possible role of this diversity in connexin expression is that regulated hetero-oligomerization of different isotypes may in turn regulate tissue function
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