Abstract
Natural resistance-associated macrophage protein 1 (NRAMP1) containing 548 amino acids (AA) and 12 transmembrane domains (TMDs) is localized in membranes of lysosomes. Our study aimed to investigate the targeting motifs of NRAMP1 by expressing GFP-tagged full-length and truncated NRAMP1 proteins and overlapping with the lysosomal marker Lamp1-RFP in Chinese hamster ovary (CHO) cells. The NH2-terminal amino acids 73–140 region including TMD2 was essential for NRAMP1 lysosomal targeting. The AA.263–334 region containing the tyrosine-based motif 327YAPI330 targeted NRAMP1 into lysosomes. Additionally, two internal signal peptides AA.451–483 and AA.489–522 were identified as lysosomal targeting motifs. Taken together, NRAMP1 consists of multiple targeting motifs for trafficking into lysosomes.
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