Two Different Functions of Connexin43 Confer Two Different Bone Phenotypes in Zebrafish
Autor: | Shigeru Kondo, Toshihiro Aramaki, Hiroaki Yamanaka, M. Kathryn Iovine, I. Martha Skerrett, Akihiro Misu, Masakatsu Watanabe |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Patch-Clamp Techniques Positional cloning Mutant Blotting Western Xenopus Connexin Biology Biochemistry Membrane Potentials Animals Genetically Modified 03 medical and health sciences Xenopus laevis 0302 clinical medicine Osteogenesis Animals Molecular Biology Zebrafish Bone growth Genetics Bone Development Wild type Gap junction Cell Biology Zebrafish Proteins biology.organism_classification Cell biology 030104 developmental biology Phenotype Microscopy Fluorescence Connexin 43 Larva Mutation cardiovascular system Animal Fins Oocytes Female sense organs biological phenomena cell phenomena and immunity 030217 neurology & neurosurgery Developmental Biology |
Zdroj: | The Journal of biological chemistry. 291(24) |
ISSN: | 1083-351X |
Popis: | Fish remain nearly the same shape as they grow, but there are two different modes of bone growth. Bones in the tail fin (fin ray segments) are added distally at the tips of the fins and do not elongate once produced. On the other hand, vertebrae enlarge in proportion to body growth. To elucidate how bone growth is controlled, we investigated a zebrafish mutant, steopsel (stp(tl28d)). Vertebrae of stp(tl28d) (/+) fish look normal in larvae (∼30 days) but are distinctly shorter (59-81%) than vertebrae of wild type fish in adults. In contrast, the lengths of fin rays are only slightly shorter (∼95%) than those of the wild type in both larvae and adults. Positional cloning revealed that stp encodes Connexin43 (Cx43), a connexin that functions as a gap junction and hemichannel. Interestingly, cx43 was also identified as the gene causing the short-of-fin (sof) phenotype, in which the fin ray segments are shorter but the vertebrae are normal. To identify the cause of this difference between the alleles, we expressed Cx43 exogenously in Xenopus oocytes and performed electrophysiological analysis of the mutant proteins. Gap junction coupling induced by Cx43(stp) or Cx43(sof) was reduced compared with Cx43-WT. On the other hand, only Cx43(stp) induced abnormally high (50× wild type) transmembrane currents through hemichannels. Our results suggest that Cx43 plays critical and diverse roles in zebrafish bone growth. |
Databáze: | OpenAIRE |
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