Novel Regulation of Fibroblast Growth Factor 2 (FGF2)-mediated Cell Growth by Polysialic Acid

Background: Polysialylated neuropilin-2 mediates CCL21-driven chemotactic migration of dendritic cells. Results: Deletion of either ST8SiaIV or O-glycosylation sites located between b2 and c domain abrogates polysialylation of neuropilin-2. Conclusion: Polysialylation of neuropilin-2 occurs in the same linker region as GAGylation of neuropilin-1. Significance: Defining enzyme and acceptor site requirements is crucial for understanding how polysialylation of neuropilin-2 is regulated.

“…However, as highlighted for FGF2 bound to heparan sulfate and polySia, the type of carbohydrate chain will determine how a soluble factor is displayed (72).…”

Section: Discussionmentioning

confidence: 99%

Polysialic Acid on Neuropilin-2 Is Exclusively Synthesized by the Polysialyltransferase ST8SiaIV and Attached to Mucin-type O-Glycans Located between the b2 and c Domain

Rollenhagen¹,

Buettner²,

Reismann³

et al. 2013

“…-Recently, we demonstrated that polySia binds neurobiologically active molecules, such as BDNF, FGF2, and neurotransmitters (8,9,11). Here, we first attempted to confirm if polySia on microglia also captures BDNF.…”

Section: Polysia Captures Bdnf Which Is Released Via Degradation Of mentioning

confidence: 99%

“…The unique polySia glycotope has been considered to inhibit cellcell interactions through its anti-adhesive effects (7). Recently, polySia also functions as a reservoir for neurobiologically active molecules such as BDNF, FGF2, and neurotransmitters (8,9), regulating their availability and concentrations in the brain. In addition, relationships between altered polySia and schizophrenia have been reported (10 -12).…”

mentioning

confidence: 99%

Rapid Trimming of Cell Surface Polysialic Acid (PolySia) by Exovesicular Sialidase Triggers Release of Preexisting Surface Neurotrophin

Sumida

Hane

Yabe

et al. 2015

Self Cite

Background:Although polySia is known to retain neurotrophins, their releasing mechanism remains unknown. Results: PolySia present on the cell surface of microglia is rapidly cleared by Neu1 sialidase on exovesicles secreted upon inflammatory stimulus, leading to neurotrophin release. Conclusion: Exovesicular Neu1 regulates rapid turnover of polySia and concomitant neurotrophin function. Significance: First demonstration of on-site turnover of polySia and its physiological significance.

“…Conversely, decreased expression of polysialylated NCAM is associated with certain neuropsychiatric disorders, including schizophrenia (14). Studies by Sato, Kitajima, and colleagues (15)(16)(17) suggest why this might be the case. They were the first to demonstrate that polySia binds neurotrophic factors, neurotransmitters, and growth factors, and their work suggests that the presence of polySia can modulate signaling by these molecules.…”

mentioning

confidence: 99%

The Polysialyltransferases Interact with Sequences in Two Domains of the Neural Cell Adhesion Molecule to Allow Its Polysialylation

Thompson¹,

Foley²,

Colley

2013

Background: Recognition of the protein substrate is the first step in polysialylation of its glycans. Results: Residues in the OCAM Ig5 domain are non-permissive for its polysialylation. Conclusion:The polysialyltransferases interact with residues in both the Ig5 and FN1 domains of NCAM to allow its polysialylation. Significance: A two-domain polysialyltransferase recognition site may be required for all polysialylated proteins.