Connexins are central components of the gap junctions that allow neighbouring cells to communicate. But do they have other, gap-junction-independent, roles? To answer this question, Jean Jiang and colleagues have examined the role of the three connexins in the chick lens, where expression of Cx45.6 (but not Cx43 or Cx56) stimulates lens epithelial-fibre differentiation (see ). The authors use retroviruses to overexpress Cx45.6 constructs containing mutations that compromise gap junctions in lens primary cultures. They report that, although the mutant proteins do not form functional gap junctions, their overexpression nevertheless increases epithelial-fibre differentiation – just like wild-type Cx45.6. A chimeric protein in which the C-terminal domain of Cx45.6 replaces the equivalent domain of Cx56 can do the same. However, the authors report, neither a Cx45.6 mutant that lacks its C-terminal domain nor a chimeric Cx45.6 that contains the C-terminus of Cx56 stimulates differentiation. Thus, they conclude, the C-terminal domain of Cx45.6 plays a gap-junction-independent role in lens epithelial-fibre differentiation, possibly by relaying signals to specific cytosolic proteins with which it interacts.
