Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Laird, Dale W.

Abstract

The connexin 31 (Cx31) mutants L135V and L209F are linked to the skin disease erythrokeratodermia variabilis et progressiva. We investigated the life-cycle of Cx31 and its interplay with co-expressed Cx26, Cx30 and Cx43 in rat epidermal keratinocytes. We demonstrated that the apparent half-life of Cx31 was extended compared to Cx43, and that Cx31 gap junctions persisted longer at the cell surface. In REKs, Cx31 gap junctions were dynamic and the ablation of Cx43 did not prevent Cx31 gap junction formation. Furthermore, Cx31 and Cx30 localized to the same gap junctions and exhibited the highest correlation coefficient. Lastly, we demonstrated that the L209F and L135V mutants did not form gap junctions and induced cell death. Together, our findings suggest Cx31 exhibits a longer half-life than most connexins and that the L209F and L135V mutants cause EKVP through mechanisms that include the loss of Cx31 gap junction intercellular communication and keratinocyte death.

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Cell Biology Commons

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