Transgenic expression of endoplasmic reticulum proteins in neurons is prone to causing ER stress.

In studying the endomembrane system, organelle-specific markers tagged with fluorescent proteins are used to visualize individual organelles. However, whether the expression of organelle marker perturbs the organelle's biology is not always apparent. We report that expression of a GFP-tagged Endoplasmic Reticulum (ER) protein causes low levels of ER stress that are challenging to detect in control animals. This stress is revealed only once the ER-associated degradation (ERAD) pathway is compromised. Our results highlight the vulnerability of the ER and suggest that the possible contribution of ER stress to phenotypes obtained with transgenic markers should be considered when interpreting the phenotypes.