The sugar code in neuronal physiology

Abstract

Carbohydrate-related interactions are necessary for the correct development and function of the nervous system. As we illustrate with several examples, those interactions are controlled by carbohydrate-modifying enzymes and by carbohydrate-binding proteins that regulate a plethora of complex axonal processes. Among others, glycan-related proteins as sialidase Neu3 or galectins-1, -3, and -4 play central roles in the determination of axonal fate, axon growth, guidance and regeneration, as well as in polarized axonal glycoprotein transport. In addition, myelination is also highly dependent on glycans, and the stabilization of myelin architecture requires the interaction of the myelin-associated glycoprotein (siglec-4) with gangliosides in the axonal membrane. The roles of glycans in neuroscience are far from being completely understood, though the cases presented here underscore the importance and potential of carbohydrates to establish with precision key molecular mechanisms of the physiology of the nervous system. New specific applications in diagnosis as well as the definition of new molecular targets to treat neurological diseases related to lectins and/or glycans are envisioned in the future.

Sialylation of N-glycans: mechanism, cellular compartmentalization and function

“…Interestingly, polySia is also being used as a less immunogenic and more biodegradable substitute for polyethylene glycol (PEG) to enhance the stability and circulating half-life of therapeutic proteins [reviewed in Bader and Wardwell (2014), Colley et al (2014)], and as part of nanoparticles for drug delivery (Zhang et al 2014(Zhang et al , 2016. Please see below for a discussion of the protein specificity of polysialylation, its role cancer, and the article in this issue by Higuero and colleagues that discusses the role of glycans, including polySia, in CNS and PNS development and function (Higuero et al 2017).…”

“…NEU3 is localized to plasma membrane and exclusively hydrolyzes Sias on gangliosides, preferring either the α2,3or α2,8-linkages found in GM3 and GD3 gangliosides. Interestingly, the ability of NEU3 to convert GT1b and GD1a to monosialic GM1 plays a role in axon growth and regeneration (reviewed in (Higuero et al 2017) in this issue). See also the article by Kopitz (2017) in this issue for more information on glycolipids and the article by Kaltner et al (2017) in this issue on the functional consequences of galectin binding to glycolipids once Sia is removed.…”

Network analysis of adhesion/growth‐regulatory galectins and their binding sites in adult chicken retina and choroid

“…Initially viewed as a rather inert appendix to proteins (Sharon & Lis, 1997;Reuter & Gabius, 1999), these glycan chains are being increasingly determined to have a salient biological meaning. In fact, it has become clear that carbohydrates, the third alphabet of life after nucleotides and amino acids, can be considered 'letters' in which to store biorelevant information at high coding capacity in oligosaccharides or glycans ('words') (Gahmberg & Tolvanen, 1996;Spiro, 2002;Cummings, 2009;Gabius, 2009Gabius, , 2015Moremen et al 2012;Corfield & Berry, 2015;Sol ıs et al 2015;Corfield, 2017;Gabius & Roth, 2017;Higuero et al 2017). As a consequence, we are beginning 'to appreciate how deeply glycan functions pervade all aspects of organismic biology, molecular biology, and biochemistry' (Hart, 2013).…”

Analyzing epigenetic control of galectin expression indicates silencing of galectin‐12 by promoter methylation in colorectal cancer

“…Finally, also variations in the non‐CRD part within one basic structure, for example, the linker region in tandem repeat galectins, may cause striking differences in sugar binding. Altogether, these fine‐tuned binding characteristics provide the molecular basis for the specific influence of individual galectins on the control of diverse physiological and pathological processes, including cell‐cell and cell‐matrix interaction, growth, and differentiation control, apoptosis, immune and inflammatory responses, neural repair and degeneration, and tumor development and progression .…”