Retrieval of transmembrane proteins to the endoplasmic reticulum.

TLDR

A COOH‑terminal double lysine motif retains type I transmembrane proteins in the ER, and its retrieval efficiency depends on sequence context, with initiation possible at multiple points along the exocytotic pathway. Proteins bearing the motif, such as CD8/E19 and CD4/E19, acquire intermediate‑compartment post‑translational modifications rapidly and Golgi‑type modifications more slowly, and lectin staining shows these Golgi‑modified proteins localize to the ER, confirming the motif as a retrieval signal.

Abstract

A COOH-terminal double lysine motif maintains type I transmembrane proteins in the ER. Proteins tagged with this motif, eg., CD8/E19 and CD4/E19, rapidly receive post-translational modifications characteristic of the intermediate compartment and partially colocalized to this organelle. These proteins also received modifications characteristic of the Golgi but much more slowly. Lectin staining localized these Golgi modified proteins to ER indicating that this motif is a retrieval signal. Differences in the subcellular distribution and rate of post-translational modification of CD8 maintained in the ER by sequences derived from a variety of ER resident proteins suggested that the efficiency of retrieval was dependent on the sequence context of the double lysine motif and that retrieval may be initiated from multiple positions along the exocytotic pathway.