In vivo heteromer formation. Expression of soluble βA4-crystallin requires coexpression of a heteromeric partner

Abstract

The β-crystallins are a family of long-lived, abundant structural proteins that are coexpressed in the vertebrate lens. As β-crystallins form heteromers, a process that involves transient exposure of hydrophobic interfaces, we have examined whether in vivo β-crystallin assembly is enhanced by protein chaperones, either small heat shock proteins, Hsp27 or αB-crystallin, or Hsp70. We show here that βA4-crystallin is abundantly expressed in HeLa cells, but rapidly degraded, irrespective of the presence of Hsp27, αB-crystallin or Hsp70. Degradation is even enhanced by Hsp70. Coexpression of βA4-crystallin with βB2-crystallin yielded abundant soluble βA4-βB2-crystallin heteromers; βB1-crystallin was much less effective in solubilizing βA4-crystallin. As βB2-crystallin competed for βA4-crystallin with Hsp70 and the proteasomal degradation pathway, βB2-crystallin probably captures an unstable βA4-crystallin intermediate. We suggest that the proper folding of βA4-crystallin is not mediated by general chaperones but requires a heteromeric partner, which then also acts as a dedicated chaperone towards βA4-crystallin. © 2006 The Authors.