Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Neuroscience

Supervisor

Donglin Bai

Abstract

Two hexameric connexin hemichannels dock together to from a whole gap junction (GJ) channel. The mechanisms of docking specificity in forming homotypic and heterotypic GJ channels are not fully clear. To reveal the key differences between Cx26 and Cx43 (or Cx40) in their docking residues, we aligned and analyzed ten well studied connexin sequences. Five of them are docking compatible with Cx26 and the rest (including Cx43 and Cx40) are not. According to Cx26 crystal structure at the docking interface, we identified two putative docking residues on the second extracellular domain (E2) that are well conserved within docking compatible connexins, but drastically different between docking incompatible connexins. Switching both of these residues in Cx26 into the corresponding residues in the docking incompatible connexins (K168V-N176H) established morphological and functional heterotypic GJs with Cx43 (or Cx40), indicating these two residues are important for docking incompatibility of these and likely other related connexins.


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