Transcriptomics of a KDELR1-KO cell line reveals defects in ECM formation and modulated cell adhesion properties

KDELRs represent transmembrane proteins of the secretory pathway which regulate the retention of soluble ER-residents as well as retrograde and anterograde trafficking processes. Additionally, they are involved in the regulation of cellular stress responses and ECM degradation. To get insights into KDELR1 specific functions, we characterized a KDELR1-KO cell line (HAP1) and performed a whole transcriptome analysis comparing KDELR1-KO and the respective wildtype HAP1 cells. Our data indicates more than 300 significantly differentially expressed genes which are mainly associated with developmental processes, cell adhesion and ECM composition point to severe cellular disorders due to KDELR1 loss. Impaired adhesion capacity of KDELR1-KO cells was further confirmed by adhesion assays and might be caused by deficient ECM formation due to transport defects. Thus, ECM rescue by collagen- and laminin-coating nearly doubled the adhesion property of KDELR1-KO cells compared to wildtype, confirming transcriptional adaptation to improve the adhesion ability. Perturbations within the secretory pathway were further verified by an increased secretion of ER-resident PDI and decreased cell viability under ER stress conditions, suggesting strong difficulties for KDELR1-KO cells to maintain cellular homeostasis.