Intracellular targeting of Cisd2/Miner1 to the endoplasmic reticulum

Background Cisd1 and Cisd2 proteins share very similar structures with an N-terminal membrane-anchoring domain and a C-terminal cytosolic domain containing an iron-cluster binding domain and ending with a C-terminal KKxx sequence. Despite sharing a similar structure, Cisd1 and Cisd2 are anchored to different compartments: mitochondria for Cisd1 and endoplasmic reticulum for Cisd2. The aim of this study was to identify the protein motifs targeting Cisd2 to the ER and ensuring its retention in this compartment. Results We used new recombinant antibodies to localize Cisd1 and Cisd2 proteins, as well as various protein chimeras. Cisd2 is targeted to the ER by its N-terminal sequence. It is then retained in the ER by the combined action of a C-terminal COPI-binding KKxx ER retrieval motif, and of an ER-targeting transmembrane domain. As previously reported for Cisd1, Cisd2 can alter the morphology of the compartment in which it accumulates. Conclusion Although they share a very similar structure, Cisd1 and Cisd2 use largely different intracellular targeting motifs to reach their target compartment (mitochondria and endoplasmic reticulum, respectively).

Automated summary

Cisd1 and Cisd2, despite their similar structures, use different intracellular targeting motifs to reach their respective compartments (mitochondria and endoplasmic reticulum). Cisd2 is targeted to the ER by its N-terminal sequence, and retained by a C-terminal COPI-binding KKxx ER retrieval motif and an ER-targeting transmembrane domain. Both Cisd1 and Cisd2 can alter the morphology of the compartments in which they accumulate.