Intermediate filaments are generally regarded as one of the most insol
uble and resilient cytoskeletal structures of eukaryotic cells. In ext
racts from the ocular lens, we noticed an unusually high level of vime
ntin in a soluble, non-filamentous form. Immunoprecipitation of this s
oluble vimentin resulted in the co-precipitation of alpha-crystallins.
The alpha-crystallins are homologous to the small heat shock proteins
(sHSPs) and have recently been identified as molecular chaperones, ca
pable of preventing the heat-induced aggregation of proteins. We find
that the alpha-crystallins dramatically inhibit the in vitro assembly
of GFAP and vimentin in an ATP-independent manner. This inhibition is
also independent of the phosphorylation state of the alpha-crystallin
polypeptides and each one of the four polypeptides, either alpha A1-,
alpha A2, alpha B1- or alpha B2-crystallin, are equally effective in t
his inhibition. Furthermore, we show that alpha-crystallins can increa
se the soluble pool of GFAP when added to preformed filaments. Electro
n microscopy demonstrated that alpha-crystallin particles could bind t
o intermediate filaments in a regular fashion, the spacing coinciding
with the molecular length of GFAP. This is the first report, as far as
we are aware, of a chaperone being involved in intermediate filament
assembly and implicates chaperones in the remodelling of intermediate
filaments during development and cell differentiation.