Cellular translocation and secretion of sialidases

Abstract

Sialidases (or neuraminidases) catalyze the hydrolysis of sialic acid (Sia)-containing molecules, mostly the removal of the terminal Sia on glycans (desialylation) of either glycoproteins or glycolipids. Therefore, sialidases can modulate the functionality of the target glycoprotein or glycolipid and are involved in various biological pathways in health and disease. In mammalian cells, there are four kinds of sialidase, which are Neu1, Neu2, Neu3, and Neu4, based on their subcellular locations and substrate specificities. Neu1 is the lysosomal sialidase, Neu2 is the cytosolic sialidase, Neu3 is the plasma membrane-associated sialidase, and Neu4 is found in the lysosome, mitochondria, and endoplasmic reticulum. In addition to specific subcellular locations, sialidases can translocate to different subcellular localizations within particular cell conditions and stimuli, thereby participating in different cellular functions depending on their loci. Lysosomal sialidase Neu1 can translocate to the cell surface upon cell activation in several cell types, including immune cells, platelets, endothelial cells, and epithelial cells, where it desialylates receptors and thus impacts receptor activation and signaling. On the other hand, cells secrete sialidases upon activation. Secreted sialidases can serve as extracellular sialidases and cause the desialylation of both extracellular glycoproteins or glycolipids and cell surface glycoproteins or glycolipids on their own and other cells, thus playing roles in various biological pathways as well. This review discusses the recent advances and understanding of sialidase translocation in different cells and secretion from different cells under different conditions and their involvement in physiological and pathological pathways.

Keywords: desialylation; exosome; sialic acid; sialidase; sialylation.

Figure 1

Sialic acids (Sias), sialylation, and desialylation of cell surface glycoprotein and glycolipid by sialidase.

Figure 2

Subcellular distribution of sialidases and their translocations. Neu1 is typically located in the lysosome and can translocate to the cell surface, Neu2 in cytosol can translocate to the cell surface, Neu3 on the plasma membranes can translocate to the endosome, while Neu4 is located in lysosome, mitochondria, and endoplasmic reticulum and can translocate to the cell surface as well.

Figure 3

The cell secretes sialidase and secretedsialidase serves as an extracellular sialidase. Secreted sialidase causes the desialylation of cell surface glycoprotein and glycolipid of its own (A), extracellular glycoprotein and glycolipid (B), and cell surface glycoprotein and glycolipid of adjacent same (C) and different (D) cell.