BIP AND CALRETICULIN FORM AN ABUNDANT COMPLEX THAT IS INDEPENDENT OF ENDOPLASMIC-RETICULUM STRESS

BiP is found in association with calreticulin, both in the presence an d absence of endoplasmic reticulum stress. Although the BiP-calreticul in complex can be disrupted by ATP, several properties suggest that th e calreticulin associated with BiP is neither unfolded nor partially o r improperly folded. (1) The complex is stable in vivo and does not di ssociate during 8 hr of chase. (2) When present in the complex, calret iculin masks epitopes at the C terminus of BiP that are not masked whe n Dip is bound to an assembly-defective protein. And (3) overproductio n of calreticulin does not lead to the recruitment of more BiP into co mplexes with calreticulin. The BiP-calreticulin complex can be disrupt ed by low pH but not by divalent cation chelators. When the endoplasmi c reticulum retention signal of Dip is removed, complex formation with calreticulin still occurs, and this explains the poor secretion of th e truncated molecule. Gel filtration experiments showed that BiP and c alreticulin are present in distinct high molecular weight complexes in which both molecules interact with each other. The possible functions of this complex are discussed.