Monocyte differentiation up-regulates the expression of the lysosomal sialidase, Neu1, and triggers its targeting to the plasma membrane via major histocompatibility complex class II-positive compartments.
Human sialidase (neuraminidase) Neu1 catalyzes lysosomal catabolism of sialylated glycoconjugates. Here we show that during the differentiation of monocytes and the monocytic cell line, THP-1, into macrophages, the majority of Neu1 relocalizes from the lysosomes to the cell surface. In contrast to other cellular sialidases Neu2, Neu3, and Neu4, whose expression either remains unchanged or is down-regulated, Neu1 mRNA, protein and activity are specifically increased during the phorbol 12-myristate 13-acetate-induced differentiation, consistent with a significant induction of the transcriptional activity of the Neu1 gene promoter. The lysosomal carboxypeptidase, cathepsin A, which forms a complex with and activates Neu1 in the lysosome, is sorted to the plasma membrane of the differentiating cells similarly to Neu1. Both proteins are first targeted to the lysosome and then are sorted to the LAMP-2-negative, major histo-compatibility complex II-positive vesicles, which later merge with the plasma membrane. Similar trafficking was observed for the internalized fluorescent dextran or horseradish peroxidase initially stored in the lysosomal/endosomal compartment. The suppression of Neu1 expression in the THP-1-derived macrophages by small interfering RNA or with anti-Neu1 antibodies significantly reduced the ability of the cells to engulf bacteria or to produce cytokines. Altogether our data suggest that the upregulation of the Neu1 expression is important for the primary function of macrophages and establish the link between Neu1 and the cellular immune response.
Liang
Feng
F
Sainte-Justine Hospital and the Department of Pediatrics, University of Montreal, Montreal, Quebec H3T 1C5, Canada.
Seyrantepe
Volkan
V
Landry
Karine
K
Ahmad
Rasheed
R
Ahmad
Ali
A
Stamatos
Nicholas M
NM
Pshezhetsky
Alexey V
AV
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005802:Genes, MHC Class II; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008264:Macrophages / Q000378:metabolism*; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D009439:Neuraminidase / Q000737:chemistry* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
C486385:NEU1 protein, human; D009439:Neuraminidase