Deciphering functional glycosaminoglycan motifs in development

Townley, Robert; Bülow, Hannes E.

doi:10.1016/j.sbi.2018.03.011

Cited by 40 publications

(35 citation statements)

References 96 publications

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“…The role of CSs in treating arthritis and related conditions is well studied . More recently, specific cellular functions of CS oligosaccharides have been uncovered . Apart from commercial applications, both the CS polysaccharides as well as CS‐derived oligosaccharides find much use in research today.…”

Section: Introductionmentioning

confidence: 99%

Increased 3′‐Phosphoadenosine‐5′‐phosphosulfate Levels in Engineered Escherichia coli Cell Lysate Facilitate the In Vitro Synthesis of Chondroitin Sulfate A

Badri

Williams

Xia

et al. 2019

Biotechnology Journal

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Chondroitin sulfates (CSs) are linear glycosaminoglycans that have important applications in the medical and food industries. Engineering bacteria for the microbial production of CS will facilitate a one‐step, scalable production with good control over sulfation levels and positions in contrast to extraction from animal sources. To achieve this goal, Escherichia coli (E. coli) is engineered in this study using traditional metabolic engineering approaches to accumulate 3′‐phosphoadenosine‐5′‐phosphosulfate (PAPS), the universal sulfate donor. PAPS is one of the least‐explored components required for the biosynthesis of CS. The resulting engineered E. coli strain shows an ≈1000‐fold increase in intracellular PAPS concentrations. This study also reports, for the first time, in vitro biotransformation of CS using PAPS, chondroitin, and chondroitin‐4‐sulfotransferase (C4ST), all synthesized from different engineered E. coli strains. A 10.4‐fold increase is observed in the amount of CS produced by biotransformation by employing PAPS from the engineered PAPS‐accumulating strain. The data from the biotransformation experiments also help evaluate the reaction components that need improved production to achieve a one‐step microbial synthesis of CS. This will provide a new platform to produce CS.

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Section: Introductionmentioning

confidence: 99%

Increased 3′‐Phosphoadenosine‐5′‐phosphosulfate Levels in Engineered Escherichia coli Cell Lysate Facilitate the In Vitro Synthesis of Chondroitin Sulfate A

Badri

Williams

Xia

et al. 2019

Biotechnology Journal

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“…They are also modulating cytokine activity and availability by sequestering them and are bringing a higher level of subtlety to the cellular response (Figure 4). Moreover, the presence of distinct and precise GAG motifs is involved in specific functions in different cellular contexts [169]. On the left panel, GAG side chains and the tyrosine sulfate-rich domain of SLRPs help to maintain the ECM biomechanical properties and the fibrillogenesis and organize the collagen fibrils.…”

Section: Discussionmentioning

confidence: 99%

From Translation to Protein Degradation as Mechanisms for Regulating Biological Functions: A Review on the SLRP Family in Skeletal Tissues

Zappia¹,

Joiret

Sanchez³

et al. 2020

Biomolecules

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The extracellular matrix can trigger cellular responses through its composition and structure. Major extracellular matrix components are the proteoglycans, which are composed of a core protein associated with glycosaminoglycans, among which the small leucine-rich proteoglycans (SLRPs) are the largest family. This review highlights how the codon usage pattern can be used to modulate cellular response and discusses the biological impact of post-translational events on SLRPs, including the substitution of glycosaminoglycan moieties, glycosylation, and degradation. These modifications are listed, and their impacts on the biological activities and structural properties of SLRPs are described. We narrowed the topic to skeletal tissues undergoing dynamic remodeling.

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“…These, and newer interaction networks (Leyva-Diaz et al 2014;Jaworski et al 2015) are continually being discovered, and how they can all coordinate in such a highly cooperative manner is fascinating. In addition, the role of proteoglycans in Slit-Robo and development signaling pathways adds yet another layer of complexity (Townley and Bülow 2018). The interplay and communication between the major neuronal receptor classes is fast becoming an important research focus in the neurobiology field, and many examples now exist, such as the recently reported Robo1-Dscam1 co-receptor complex that is mediated by Slit2-N (Alavi et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Structure and Function of Roundabout Receptors

Bisiak

McCarthy

2019

Subcellular Biochemistry

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The creation of complex neuronal networks relies on ligand-receptor interactions that mediate attraction or repulsion towards specific targets. Roundabouts comprise a family of single-pass transmembrane receptors facilitating this process upon interaction with the soluble extracellular ligand Slit protein family emanating from the midline. Due to the complexity and flexible nature of Robo receptors, their overall structure has remained elusive until now. Recent structural studies of the Robo1 and Robo2 ectodomains have provided the basis for a better understanding of their signalling mechanism. These structures reveal how Robo receptors adopt an auto-inhibited conformation on the cell surface that can be further stabilised by cis and/or trans oligmerisation arrays. Upon Slit-N binding Robo receptors must undergo a conformational change for Ig4 mediated dimerisation and signaling, probably via endocytosis. Furthermore, it's become clear that Robo receptors do not only act alone, but as large and more complex cell surface receptor assemblies to manifest directional and growth effects in a concerted fashion. These context dependent assemblies provide a mechanism to fine tune attractive and repulsive signals in a combinatorial manner required during neuronal development. While a mechanistic understanding of Slit mediated Robo signaling has advanced significantly further structural studies on larger assemblies are required for the design of new experiments to elucidate their role in cell surface receptor complexes. These will be necessary to understand the role of Slit-Robo signaling in neurogenesis, angiogenesis, organ development and cancer progression. In this chapter, we provide a review of the current knowledge in the field with a particular focus on the Roundabout receptor family.

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Deciphering functional glycosaminoglycan motifs in development

Cited by 40 publications

References 96 publications

Increased 3′‐Phosphoadenosine‐5′‐phosphosulfate Levels in Engineered Escherichia coli Cell Lysate Facilitate the In Vitro Synthesis of Chondroitin Sulfate A

Increased 3′‐Phosphoadenosine‐5′‐phosphosulfate Levels in Engineered Escherichia coli Cell Lysate Facilitate the In Vitro Synthesis of Chondroitin Sulfate A

From Translation to Protein Degradation as Mechanisms for Regulating Biological Functions: A Review on the SLRP Family in Skeletal Tissues

Structure and Function of Roundabout Receptors

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