the transverse tubule compared to the wild-type and controls. Moreover, aggregations of degenerative membrane proteins were observed in the expanded SR. This suggests that the mutant KDEL receptor leads to impaired recycling and quality control of the ER, which leads to aggregation of misfolded proteins in the ER. Furthermore, KDEL D193N transgenic mice had defects in the L-type Ca++ channel current in ventricular myocytes. The basal current of these channels was significantly lower than the controls. L-type channels expression was lower in the plasma membrane of the KDEL D193N heart cells due to the narrowing of transverse tubules. BiP, a chaperone protein, was unevenly distributed and synthesized in larger proportion in the transgenic mutant mice, which suggests that there was an increase in concentration of misfolded proteins. They also observed aggregates of the ubiquitin-proteasome system (a degradation system); this suggests that there was saturation of the system due to the high levels of misfolded proteins that lead to impaired ER quality control. The researchers concluded that hyperubiquitination and saturation of the proteasome system results due to the accumulation of misfolded protein, which induces stress. The accumulation of misfolded proteins induced by ER stress has also been observed in human DCM. A murine DCM study found an increase in apoptosis due to the high levels of CHOP expression. CHOP is a transcription factor that is elevated during ER stress and causes apoptosis of cells during the process of an unfolded protein response. Increase pressure load/mechanical stress in KDEL D193N mice caused an even greater synthesis of BiP, CHOP and other proteins that are biomarkers of cellular stress and ER stress as the capacity of the ER to deal with this is very limited. Lymphopenia KDELR1 is also critical for the development of lymphocytes. Mice with a Y158C missense mutation in Kdelr1 have reduced numbers of B and T lymphocytes, and a more susceptible to viral infection. Interactions KDELR1 has been shown to interact with ARFGAP1. Structure The structure of Gallus gallus KDELR2 (Uniprot Q5ZKX9) has been solved in the Apo state, KDEL peptide-bound state, and bound to a synthetic nanobody. Sequence identity between human KDELR1 and chicken KDELR2 is 84.4%. See also KDELR2 KDELR3 References Further reading Endoplasmic reticulum resident proteins