Functional Consequences of Keratan Sulfate Sulfation in Electrosensory Tissues and in Neuronal Regulation

Abstract

Keratan sulfate (KS) is a functional electrosensory and neuro‐instructive molecule. Recent studies have identified novel low sulfation KS in auditory and sensory tissues such as the tectorial membrane of the organ of Corti and the Ampullae of Lorenzini in elasmobranch fish. These are extremely sensitive proton gradient detection systems that send signals to neural interfaces to facilitate audition and electrolocation. High and low sulfation KS have differential functional roles in song learning in the immature male zebra song‐finch with high charge density KS in song nuclei promoting brain development and cognitive learning. The conductive properties of KS are relevant to the excitable neural phenotype. High sulfation KS interacts with a large number of guidance and neuroregulatory proteins. The KS proteoglycan microtubule associated protein‐1B (MAP1B) stabilizes actin and tubulin cytoskeletal development during neuritogenesis. A second 12 span transmembrane synaptic vesicle associated KS proteoglycan (SV2) provides a smart gel storage matrix for the storage of neurotransmitters. MAP1B and SV2 have prominent roles to play in neuroregulation. Aggrecan and phosphacan have roles in perineuronal net formation and in neuroregulation. A greater understanding of the biology of KS may be insightful as to how neural repair might be improved.

Proteoglycans as Therapeutic Targets in Brain Cancer

“…There is significant evidence showing that the sulfate composition of CS GAG chains changes with age. As a result of aging and aggregation of proteins, the deposition of HS PGs and CS PGs results in the injury of protective perineuronal nets with increased cell death (60). Dying neurons then induce inflammation, ECM degrades through the proteolytic activity of enzymes, inducing responses that amplify neuronal death and neuroinflammation (68).…”

Electro‐Stimulation, a Promising Therapeutic Treatment Modality for Tissue Repair: Emerging Roles of Sulfated Glycosaminoglycans as Electro‐Regulatory Mediators of Intrinsic Repair Processes

“…[ 45 ] Something that also needs to be considered in these developmental tissue processes is the role of proteoglycan GAG side chains which carry counterions and their potential roles as ion reservoirs in specific developmental niches. [ 46,47 ] KS is a widely distributed GAG in sensory tissues and displays variable sulfation levels which may facilitate fine levels of control over the counterions they make available for the generation of ion channel generated events in specific developmental contexts. [ 10,24,25,48 ]…”

“…A KS substituted PG‐mucin‐like glycoconjugate gel isolated from the Ampullae of Lorenzini, a sensory pore‐like system present on the surface of the skin of elasmobranch fish species (sharks, rays, skates), is the best proton detection polymer known in Nature [ 56 ] ( Figure ). KS in such mucinous deposits equips coupled neurosensory networks in the fish skin with the ability to detect electric fields generated by the muscular activity of preyfish species, a process known as electro‐location [ 47 ] and is used to hunt prey fish under turbid water conditions of poor visibility. A similar process is used by some freshwater fish species such as the Mormyridae gymnotiform Elephant fish (genus Gnathonemus ) of the Belgian Congo or the Sternopygidae Glassknife fish ( Eigenmannia sp) of the Amazon in a process known as electro‐communication [ 57 ] ( Figure a,b).…”

“…[ 55,56,65 ] The predominance of KS substituted molecules in neural tissues also testifies to the unique functional properties conveyed by this GAG in sensory processes. [ 25,46,47,55,56 ] In weakly electric fish species which employ electro‐location or electro‐communication, a characteristic electric oscillatory discharge is generated and emitted by a pacemaker organ. This electrical discharge can be modulated in terms of its amplitude, frequency and the waveform of the signal elicited and other fish can interpret this signal which thereby forms a sophisticated means of social communication.…”

“…[ 84,136,138 ] GAGs and PEDOT‐type derivatives provide a compatible electrically conductive, hydrophilic neural interface mimicking the intrinsic electro‐conductive hydrophilic properties of KS‐PGs in neural and sensory tissues. [ 10,24,25,46,47,137,139 ] PEDOT:PSS is an electro‐conductive polymer consisting of the semi‐conductor PEDOT and the dopant PSS which raises the room temperature electrical conductivity of the PEDOT:PSS composite to high levels (100 S cm −1 , even up to 1000 S cm −1 with proper optimization).…”