PROTEO-GLYCOSAMINOGLYCANS AND THEIR IMPORTANCE

Proteoglycans and glycosaminoglycans (PGAGs) are essential macromolecules composed of proteins and glycosaminoglycans (GAGs), playing crucial roles in a variety of biological processes. These molecules are involved in cell signaling, tissue repair, regulation of cell growth, and maintaining the structural integrity of tissues. The biosynthesis of PGAGs involves a series of complex enzymatic reactions, and understanding the genes involved in this process can offer valuable insights into several diseases, including cancers, autoimmune disorders, and developmental diseases.

Role of AnyGenes qPCR Array in PGAG Research

AnyGenes qPCR arrays are an invaluable tool for studying the genes involved in PGAG biosynthesis. Our high-throughput qPCR arrays provide precise gene expression profiling, allowing researchers to identify key enzymes and regulatory genes, investigate disease mechanisms, and monitor gene expression in various tissues.

By leveraging AnyGenes qPCR solutions, researchers can enhance their studies on PGAG biosynthesis, leading to more informed insights and potential therapeutic breakthroughs.

Visual representation of key genes involved in Proteo-Glycosaminoglycans biosynthesis, analyzed using AnyGenes qPCR arrays for precise gene expression profiling.

Glycosaminoglycans biosynthesis-The biosynthetic pathways of heparan sulfate and chondroitin sulfate/dermatan sulfate.

The biosynthetic pathways of heparan sulfate and chondroitin sulfate/dermatan sulfate. HS, heparan sulfate; CS, chondroitin sulfate; DS, dermatan sulfate; 2S, 2-O-sulfation; 6S, 6-O-sulfation; 3S, 3-O-sulfation; 4S, 4-O-sulfation; NS, N-sulfated glucosamine. XylT1/2, xylosyltransferase 1/2; FAM20B, family with sequence similarity member 20-B; PXYLP1, 2-phosphoxylose phosphatase; GalT-I, galactosyltransferase-I; GalT-II, galactosyltransferase-II; GlcAT-Ⅰ, glucuronyltransferase-Ⅰ;

EXT1, exostosin glycosyltransferase 1; EXT2, exostosin glycosyltransferase 2; EXTL1, exostosin like glycosyltransferase 1; EXTL2, exostosin like glycosyltransferase 2; EXTL3, exostosin like glycosyltransferase 3; NDST1, N-sulfotransferase; NDST2, N-sulfotransferase 2; NDST3, N-sulfotransferase 3; NDST4, N-sulfotransferase 4; HS6ST1, heparan sulfate 6-O-sulfotransferase 1; HS6ST2, heparan sulfate 6-O-sulfotransferase 2; HS6ST3, heparan sulfate 6-O-sulfotransferase 3; HS3ST1, heparan sulfate 3-O-sulfotransferase 1; HS3ST2, heparan sulfate 3-O-sulfotransferase 2; HS3ST3a, heparan sulfate 3-O-sulfotransferase 3a; HS3ST3b, heparan sulfate 3-O-sulfotransferase 3b; HS3ST4, heparan sulfate 3-O-sulfotransferase 4; HS3ST5, heparan sulfate 3-O-sulfotransferase 5; HS3ST6, heparan sulfate 3-O-sulfotransferase 6;

GLCE, C-5 epimerase; HS2ST, heparan sulfate 2-O-sulfotransferase; GalNAcT- I, GalNAc transferase-I; GalNAcT- IIs, GalNAc transferase-II; GlcAT- II,β1,3-glucuronyltransferase- II; C4ST, chondroitin 4-O-sulfotransferase; C6ST,; GalNAc4S-6ST,; UST, uronyl 2-O-sulfotransferase; DSE1, DS epimerase1; DSE2, DS epimerase2; D4ST, dermatan 4-O-sulfotransferase; GalNAc4S-6ST, GalNAc 4-sulfate 6-O-sulfotransferase. Monosaccharides in this figure are represented in accordance with the symbol nomenclature for glycans (SNFG) (Varki et al., 2015).

WHAT ARE PROTEOGLYCANS?

Proteoglycans (PGs) are essential components of the extracellular matrix, composed of a core protein covalently linked to glycosaminoglycans (GAGs). GAGs are long, unbranched polysaccharides that play crucial roles in various biological processes, including cell signaling, adhesion, and the structural integrity of tissues.

Types of glycosaminoglycans

Chondroitin Sulfate (CS)
Dermatan Sulfate (DS)
Heparan Sulfate (HS)
Keratan Sulfate (KS)
Hyaluronic Acid (not covalently attached to proteins)

Each GAG type has distinct biosynthetic pathways and functions, significantly influenced by the specific genes involved in their synthesis.

BIOSYNTHESIS PATHWAY

The biosynthesis of GAGs involves several key steps and enzymes:

Initiation: The process begins with the addition of xylose to serine residues on core proteins by xylosyltransferases (XT1 or XT2), forming a tetrasaccharide linker region: GlcAβ1 - 3Galβ1 - 4Xylβ1 - O - Ser.
Elongation: Subsequent addition of sugars is mediated by various glycosyltransferases. For instance, galactosyltransferases add galactose residues, while glucuronyltransferases contribute glucuronic acid.
Sulfation: The final modifications include sulfation, which is critical for the biological activity of GAGs. This process is facilitated by sulfotransferases that utilize 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as a sulfate donor.

GLYCOSAMINOGLYCANS EXAMPLES

More than 50 genes are implicated in GAG biosynthesis, including:

B3GALT7/B3GALT6: Involved in adding galactose to the growing chain.
B3GAT3: Encodes a glucuronyltransferase essential for completing the tetrasaccharide linker.
CSGALNACT1/CSGALNACT2: Initiate chondroitin sulfate synthesis from the linker region.
Core proteins synthesis: These genes code for the core proteins to which glycosaminoglycans are attached. Examples include AGC1 (Aggrecan Core Protein) and VCAN (Versican).
Glycosaminoglycan chain formation: The formation of GAGs involves enzymes such as EXTL3 and XYLT1/XYLT2, which are responsible for initiating glycosaminoglycan chain elongation and modification.
Enzymes for modification and sulfation: Genes involved in the modification and sulfation of PGAGs include NDST1 (N-deacetylase/N-sulfotransferase) and CHSY1 (Chondroitin Sulfate Synthase 1), which play a pivotal role in creating the structural diversity necessary for their biological functions.
Regulatory Genes: These genes regulate the activity and expression of PGAG biosynthesis enzymes. Examples include HSPG2 (Heparan Sulfate Proteoglycan 2), which regulates the synthesis of heparan sulfate PGAGs.

ROLE IN DISEASES

Defects in PGAG biosynthesis can lead to a range of disorders. Genetic mutations affecting the enzymes responsible for GAG synthesis have been linked to conditions such as: Skeletal Dysplasias, Cognitive Impairments, Cancer, Osteoarthritis, Neurological Disorders.

Therapeutic implications

Research has shown that abnormalities in PGAGs can affect cell proliferation, migration, and adhesion, contributing to disease progression. Understanding PGAG biosynthesis opens avenues for therapeutic interventions. Targeting specific enzymes involved in GAG synthesis may provide strategies for treating related disorders. For instance, enhancing or inhibiting GAG production could be explored as a therapeutic approach in cancer treatment or regenerative medicine.

(1) Sammon D, et al. Molecular mechanism of decision-making in glycosaminoglycan biosynthesis. Nat Commun. (2023)13;14(1):6425.

(2) Huang YF, et al. Novel Insight Into Glycosaminoglycan Biosynthesis Based on Gene Expression Profiles. Front Cell Dev Biol. (2021)6:9:709018.

(3) Sasarman F, et al. Biosynthesis of glycosaminoglycans: associated disorders and biochemical tests. J Inherit Metab Dis. (2016);39(2):173-88.

(4) Proteoglycans and Glycosaminoglycans. https://www.ncbi.nlm.nih.gov/books/NBK20693/

(5) Wu T, et al. The Glycosylphosphatidylinositol biosynthesis pathway in human diseases. Orphanet J Rare Dis. (2020)28;15(1):129.

(6) Chen J, et al. Proteoglycans and Glycosaminoglycans in Stem Cell Homeostasis and Bone Tissue Regeneration. Front Cell Dev Biol. (2021)30:9:760532

PROTEO-GLYCOSAMINOGLYCANS BIOSYNTHESIS BIOMARKER LIST

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You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Signaling Pathways	Product ref	Informations
Proteo-Glycosaminoglycans Biosynthesis Genes	PR1H1	List infos

Species : Mus musculus (mouse)

Signaling Pathways	Product ref	Informations
Proteo-Glycosaminoglycans Biosynthesis Genes	*******	List In progress...

Species : Rattus norvegicus (rat)

Signaling Pathways	Product ref	Informations
Proteo-Glycosaminoglycans Biosynthesis Genes	*******	List In progress...

Species : Sus Scrofa (Pig)

Signaling Pathways	Product ref	Informations
Proteo-Glycosaminoglycans Biosynthesis Genes	*******	List In progress...

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