NEU3

NEU3, also known as neuraminidase 3 or sialidase 3, is a member of the mammalian sialidase family that removes terminal sialic acid residues from glycoconjugates. It is one of the four known human neuraminidases (NEU1–NEU4) and is characterized as a membrane-associated, neutral sialidase.

Biochemical properties and substrates: NEU3 primarily desialylates glycolipids, with a particular preference for gangliosides such as GM3, as well as various glycoproteins. Its activity reduces surface sialylation on these molecules, thereby altering the composition and charge of the cell membrane glycocalyx.

Localization and function: The enzyme is associated with the plasma membrane, where its catalytic domain is oriented to the extracellular milieu. Through desialylation of cell-surface glycoconjugates, NEU3 modulates glycan-mediated interactions, receptor activation, endocytosis, and the organization of membrane microdomains, influencing multiple signaling and trafficking pathways.

Expression and regulation: NEU3 is expressed in multiple human tissues, with relatively higher levels reported in the respiratory and gastrointestinal tracts. Expression and activity can be influenced by physiological and pathological stimuli, reflecting its role in dynamic regulation of cell-surface glycans.

Clinical significance: Altered NEU3 expression or activity has been observed in various disease contexts, including cancer and inflammatory conditions. In cancer models, upregulation of NEU3 can enhance cell migration and invasive properties, while changes in desialylation can affect immune recognition and signaling.

Research and tools: NEU3 is studied using cellular overexpression or knockdown approaches, as well as recombinant enzyme assays. Small-molecule inhibitors and defined substrates are used to probe its activity and biological consequences.

See also: NEU1, NEU2, NEU4, neuraminidases.