FIGURE 1.

KDELR2 loss of function (LoF) leads to inability of heat shock protein 47 (HSP47) to dissociate from procollagen. In wildtype cells, alpha collagen fibers assemble to form procollagen. Procollagen binds HSP47 and is transferred to the Golgi apparatus where KDELR2 binds HSP47 and leads to dissociation of HSP47 from procollagen. HSP47 is recycled back to the ER. Procollagen is further processed in the Golgi and secreted into the extracellular matrix (ECM) as tropocollagen. In mutant KDELR2 cells, KDELR2 is unable to bind HSP47. HSP47 cannot dissociate from procollagen and is retained in the Golgi and not secreted into the extracellular matrix [Color figure can be viewed at wileyonlinelibrary.com]