TY - JOUR
T1 - 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
AU - Liang, Feng
AU - Seyrantepe, Volkan
AU - Landry, Karine
AU - Ahmad, Rasheed
AU - Ahmad, Ali
AU - Stamatos, Nicholas M.
AU - Pshezhetsky, Alexey V.
PY - 2006/9/15
Y1 - 2006/9/15
N2 - 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 histocompatibility 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 up-regulation of the Neu1 expression is important for the primary function of macrophages and establish the link between Neu1 and the cellular immune response.
AB - 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 histocompatibility 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 up-regulation of the Neu1 expression is important for the primary function of macrophages and establish the link between Neu1 and the cellular immune response.
UR - http://www.scopus.com/inward/record.url?scp=33748754053&partnerID=8YFLogxK
U2 - 10.1074/jbc.M605633200
DO - 10.1074/jbc.M605633200
M3 - Article
C2 - 16835219
AN - SCOPUS:33748754053
VL - 281
SP - 27526
EP - 27538
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 37
ER -