ASSOCIATION OF HSP47, GRP78, AND GRP94 WITH PROCOLLAGEN SUPPORTS THE SUCCESSIVE OR COUPLED ACTION OF MOLECULAR CHAPERONES

Hsp47, Grp78, and Grp94 have been implicated with procollagen maturati on events. In particular, Hsp47 has been shown to bind to nascent proc ollagen alpha 1 (1) chains in the course of synthesis and/or transloca tion into the endoplasmic reticulum (ER). Although, Hsp47 binding to g elatin and collagen has previously been suggested to be independent of ATP. Grp78 and Grp94 are known to dissociate from its substrates by a n ATP-dependent release mechanism. The early association of Hsp47 with procollagen and its relatively late release suggested that other chap erones, Grp78 and Grp94, interact successively or concurrently with Hs p47. Herein, we examined how these events occur in cells metabolically stressed by depletion of ATP. In cells depleted of ATP, the release o f Hsp47, Grp78, and Grp94 from maturing procollagen is delayed. Thus, in cells experiencing metabolic stress, newly synthesized procollagen unable to properly fold became stably bound to a complex of molecular chaperones. In that Hsp47, Grp 78, and Grp94 could be recovered with n ascent procollagen and as oligomers in ATP depleted cells suggests tha t these chaperones function in a series of coupled or successive react ions. (C) 1994 Wiley-Liss, Inc.