Chondroitin Sulfate Tetrasaccharides: Synthesis, Three‐Dimensional Structure and Interaction with Midkine

Solera, Cristina; Macchione, Giuseppe; Maza, Susana; Kayser, Margaret M.; Corzana, Francisco; Paz, José L. de; Nieto, Pedro M.

doi:10.1002/chem.201504440

Cited by 45 publications

(73 citation statements)

References 75 publications

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“…Chemical synthesis of CS oligosaccharides with defined sequences has recently made progresses [185, 186], opening the possibility to use those to manipulate a protein-CS interaction. Meanwhile, a better understanding of CS structure, their organization within the matrix, the mode of interaction with different types of proteins, are essential for targeting the important ECM component in the CNS.…”

Section: Resultsmentioning

confidence: 99%

Chondroitin sulfates and their binding molecules in the central nervous system

2017

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Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in the central nervous system (CNS) matrix. Its sulfation and epimerization patterns give rise to different forms of CS, which enables it to interact specifically and with a significant affinity with various signalling molecules in the matrix including growth factors, receptors and guidance molecules. These interactions control numerous biological and pathological processes, during development and in adulthood. In this review, we describe the specific interactions of different families of proteins involved in various physiological and cognitive mechanisms with CSs in CNS matrix. A better understanding of these interactions could promote a development of inhibitors to treat neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Chondroitin sulfates and their binding molecules in the central nervous system

2017

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“…They have positive charged regions that are involved in binding to highly sulfated CS chains (23, 41, 42). Their binding may reduce the electrostatic repulsion of, or induce conformational changes (43) to, CS chains and resultantly shift them to the dimeric or oligomeric form in the cell membrane (Fig. 9).…”

Section: Discussionmentioning

confidence: 99%

Role of Chondroitin Sulfate (CS) Modification in the Regulation of Protein-tyrosine Phosphatase Receptor Type Z (PTPRZ) Activity

Kuboyama

Fujikawa

Suzuki

et al. 2016

Journal of Biological Chemistry

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Protein-tyrosine phosphatase receptor type Z (PTPRZ) is predominantly expressed in the developing brain as a CS proteoglycan. PTPRZ has long (PTPRZ-A) and short type (PTPRZ-B) receptor forms by alternative splicing. The extracellular CS moiety of PTPRZ is required for high-affinity binding to inhibitory ligands, such as pleiotrophin (PTN), midkine, and interleukin-34; however, its functional significance in regulating PTPRZ activity remains obscure. We herein found that protein expression of CS-modified PTPRZ-A began earlier, peaking at approximately postnatal days 5-10 (P5-P10), and then that of PTN peaked at P10 at the developmental stage corresponding to myelination onset in the mouse brain. Ptn-deficient mice consistently showed a later onset of the expression of myelin basic protein, a major component of the myelin sheath, than wild-type mice. Upon ligand application, PTPRZ-A/B in cultured oligodendrocyte precursor cells exhibited punctate localization on the cell surface instead of diffuse distribution, causing the inactivation of PTPRZ and oligodendrocyte differentiation. The same effect was observed with the removal of CS chains with chondroitinase ABC but not polyclonal antibodies against the extracellular domain of PTPRZ. These results indicate that the negatively charged CS moiety prevents PTPRZ from spontaneously clustering and that the positively charged ligand PTN induces PTPRZ clustering, potentially by neutralizing electrostatic repulsion between CS chains. Taken altogether, these data indicate that PTN-PTPRZ-A signaling controls the timing of oligodendrocyte precursor cell differentiation in vivo, in which the CS moiety of PTPRZ receptors maintains them in a monomeric active state until its ligand binding.Myelination is an essential feature of the vertebrate nervous system that electrically insulates axons, thereby enabling the salutatory transmission of nerve impulses. Oligodendrocyte precursor cells (OPCs) 2 are the principal source of myelinating oligodendrocytes (1). Previous studies reported that protein tyrosine phosphorylation is crucially involved in the signal transduction mechanism for OPC differentiation into mature oligodendrocytes and myelin formation. FYN kinase in the Src tyrosine kinase family is the most prominent member involved in OPC differentiation and myelin formation (2). FYN activity is up-regulated during oligodendrocyte differentiation (3, 4), and Fyn-knock-out mice exhibit hypomyelination in the brain (5, 6). FYN phosphorylates p190 RhoGAP, a GTPase-activating protein (GAP) for Rho GTPase, to suppress Rho/ROCK, resulting in the maturation of oligodendrocytes and myelination (7,8).PTPRZ is the most abundant receptor-type protein-tyrosine phosphatase (RPTP) in OPCs (9, 10). PTPRZ dephosphorylates p190 RhoGAP, thereby acting as a counterpart of FYN (11,12). The amounts of myelin basic protein (MBP) and myelinated axons in the brain at postnatal day 10, when myelination occurs, are significantly higher in Ptprz-deficient mice than in wildtype animals, indicating a suppre...

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“…Risher and colleagues (2015) found that thrombospondins TSP2 and TSP4 levels increase after EtOH administration in an adolescent binge‐like protocol. Another secreted molecule, midkine, binds to chondroitin sulfate and may also play a role in synaptogenesis (Solera et al., ; Zhou et al., ). ECM remodeling after EtOH exposure may release these types of molecules that have direct effects on synaptic plasticity.…”

Section: Future Directions and Gaps In Knowledgementioning

confidence: 99%

Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder

Lasek

2016

Alcoholism Clin & Exp Res

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The brain extracellular matrix (ECM) occupies the space between cells and is involved in cell-matrix and cell-cell adhesion. However, in addition to providing structural support to brain tissue, the ECM activates cell signaling and controls synaptic transmission. The expression and activity of brain ECM components are regulated by alcohol exposure. This review will discuss what is currently known about the effects of alcohol on the activity and expression of brain ECM components. An interpretation of how these changes might promote alcohol use disorder (AUD) will be also provided. Ethanol exposure decreases levels of structural proteins involved in the interstitial matrix and basement membrane, with a concomitant increase in proteolytic enzymes that degrade these components. In contrast, ethanol exposure generally increases perineuronal net (PN) components. Because the ECM has been shown to regulate both synaptic plasticity and behavioral responses to drugs of abuse, regulation of the brain ECM by alcohol may be relevant to the development of alcoholism. Although investigation of the function of brain ECM in alcohol abuse is still in early stages, a greater understanding of the interplay between ECM and alcohol might lead to novel therapeutic strategies for treating AUD.

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Chondroitin Sulfate Tetrasaccharides: Synthesis, Three‐Dimensional Structure and Interaction with Midkine

Cited by 45 publications

References 75 publications

Chondroitin sulfates and their binding molecules in the central nervous system

Chondroitin sulfates and their binding molecules in the central nervous system

Role of Chondroitin Sulfate (CS) Modification in the Regulation of Protein-tyrosine Phosphatase Receptor Type Z (PTPRZ) Activity

Effects of Ethanol on Brain Extracellular Matrix: Implications for Alcohol Use Disorder

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