Identification and Regulation of the Eukaryotic Hyaluronate Synthase

Prehm, Peter

doi:10.1002/9780470513774.ch3

Cited by 29 publications

(16 citation statements)

References 28 publications

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“…Polymerization of HA occurs at the inner face of the plasma membrane where HAS alternatively adds UDP-GlcA and UDP-GlcNAc monomers to the reducing end of the growing polymer. As the polymerization is occurring, the non-reducing end of the sugar chain is translocated into the extracellular space through a pore in the HAS structure [21]. An intriguing question is why nature uses three different isozymes for the synthesis of HA with such a simple repeating unit.…”

Section: Biosynthesis and Degradationmentioning

confidence: 99%

Hyaluronan: A simple polysaccharide with diverse biological functions

Dicker¹,

Gurski²,

et al. 2014

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Hyaluronan (HA) is a linear polysaccharide with disaccharide repeats of D-glucuronic acid and N-acetyl-D-glucosamine. It is evolutionary conserved and abundantly expressed in the extracellular matrix (ECM), on the cell surface and even inside cells. Being a simple polysaccharide, HA exhibits an astonishing array of biological functions. HA interacts with various proteins or proteoglycans to organize the ECM and to maintain tissue homeostasis. The unique physical and mechanical properties of HA contribute to the maintenance of tissue hydration, the mediation of solute diffusion through the extracellular space and the lubrication of certain tissues. The diverse biological functions of HA are manifested through its complex interactions with matrix components and resident cells. Binding of HA with cell surface receptors activates various signaling pathways that regulate cell function, tissue development, inflammation, wound healing and tumor progression and metastasis. Taking advantage of the inherent biocompatibility and biodegradability of HA, as well as its susceptibility to chemical modification, researchers have developed various HA-based biomaterials and tissue constructs with promising and broad clinical potential. In this article, we illustrate the properties of HA from a matrix biology perspective by first introducing principles underlying the biosynthesis and biodegradation of HA, as well as the interactions of HA with various proteins and proteoglycans. We next highlight the roles of HA in physiological and pathological states, including morphogenesis, wound healing and tumor metastasis. A deeper understanding of the mechanisms underlying the roles of HA in various physiological processes can provide new insights and tools for the engineering of complex tissues and tissue models.

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Section: Biosynthesis and Degradationmentioning

confidence: 99%

Hyaluronan: A simple polysaccharide with diverse biological functions

Dicker¹,

Gurski²,

et al. 2014

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“…Thus, a sugar nucleotide is always present at the reducing end of the nascent hyaluronate chain, as in the case of a nascent polypeptide chain at the ribosome which is covalently linked with a tFWA molecule. The factor(s) leading to the termination of chain growth are not yet known (Prehm, 1983(Prehm, , 1989. The gene for hyaluronate synthase from group A streptococci has recently been cloned (DeAngelis et al, 1993;DeAngelis and Weigel, 1994).…”

Section: Structure Biosynthesis and Degradationmentioning

confidence: 99%

Proteoglycans – Structure and Functions

Kresse¹

1996

Glycosciences

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“…The most prominent components of the glycocalyx are the glycosaminoglycans (GAGs) heparan sulfate (HS), chondroitin sulfate (CS) and hyaluronan (HA). Both HS and CS are synthesized inside the Golgi apparatus, whereas HA synthases (HASs) are plasma membrane associated such that newly synthesized HA strands are extruded outside the cell [28]. There are several ways for HA to be integrated into the glycocalyx.…”

Section: Introductionmentioning

confidence: 99%

Protease activity and the role of the endothelial glycocalyx in inflammation

Lipowsky

2011

Drug Discovery Today: Disease Models

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A new paradigm for governance of leukocyte-endothelium (WBC-EC) adhesion during the inflammatory process is presented in which shedding of the endothelial glycocalyx exposes adhesion molecules on the EC surface, which promotes WBC-EC adhesion. It is postulated that the effector of this shedding is the activation of extracellular proteases, one of which may be a member of the matrix metalloproteinase (MMP) family of zinc dependent endopetidases. This model for the role of the glycocalyx as a barrier to WBC-EC adhesion includes the additional participation of normally active extracellular proteolytic enzymes, i.e. sheddases, which may cleave proteoglycans or activate lyases that cleave GAG chains in the glycocalyx. In support of this hypothesis, studies are examined which have established the concurrent activation of MMP proenzymes on the EC surface, shedding of the glycocalyx, and enhanced WBC-EC adhesion.

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Identification and Regulation of the Eukaryotic Hyaluronate Synthase

Cited by 29 publications

References 28 publications

Hyaluronan: A simple polysaccharide with diverse biological functions

Hyaluronan: A simple polysaccharide with diverse biological functions

Proteoglycans – Structure and Functions

Protease activity and the role of the endothelial glycocalyx in inflammation

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