The long signal peptide isoform and its alternative processing direct the intracellular trafficking of interleukin-15.
Two isoforms of interleukin (IL)-15 exist: one with a short and another with a long signal peptide (LSP). Experiments using combinations of the LSP and mature proteins IL-2, IL-15, and green fluorescent protein revealed complex pathways of intracellular trafficking. In one pathway, the LSP was unprocessed, and IL-15 was not glycosylated, remained in the cytoplasm, and was degraded. The second trafficking pathway involved endoplasmic reticulum entry, N-linked glycosylation, and alternative partial LSP processing. The third pathway involved endoplasmic reticulum entry, followed by glycosylation, complete processing, and ultimately secretion. The complex intracellular trafficking patterns of LSP-IL-15 with its impediments to secretion as well as impediments to translation may be required due to the potency of IL-15 as an inflammatory cytokine. In terms of a more positive role, we propose that intracellular infection may relieve the burdens on translation and intracellular trafficking to yield effective IL-15 expression.
Kurys
G
G
Metabolism Branch, NCI, National Institutes of Health and the Laboratory of Cell Biochemistry and Biology, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1374, USA.
Tagaya
Y
Y
Bamford
R
R
Hanover
J A
JA
Waldmann
T A
TA
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001681:Biological Assay; D001692:Biological Transport; D019556:COS Cells; D002451:Cell Compartmentation; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006031:Glycosylation; D006596:Hexosaminidases / Q000494:pharmacology; D019409:Interleukin-15 / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D020033:Protein Isoforms; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D021382:Protein Sorting Signals / Q000737:chemistry / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D019409:Interleukin-15; D020033:Protein Isoforms; D011498:Protein Precursors; D021382:Protein Sorting Signals; C067713:lactacystin; D006596:Hexosaminidases; D000111:Acetylcysteine