Atypical sialylated N-glycan structures are attached to neuronal voltage gated potassium channels.
Biosci Rep. 2008 Oct 21;
Authors: Cartwright TA, Schwalbe RA
Mammalian brains contain relatively high amounts of common and uncommon sialylated N-glycan structures. Sialic acid linkages were identified for voltage gated potassium channels, Kv3.1, 3.3, 3.4, 1.1, 1.2, and 1.4, by evaluating their electrophoretic migration patterns in adult rat brain membranes digested with various glycosidases. Additionally, their electrophoretic migration patterns were compared to those of N-CAM, transferrin, and the Kv3.1 protein heterologously expressed in B35 neuroblastoma cells. Metabolic labeling of the sugars combined with glycosidase digestion reactions were utilized to show that the N-glycan of recombinant Kv3.1 protein was capped with an oligo/polysialyl unit. All three brain Kv3 glycoproteins, like N-CAM, were terminated with alpha2,3-linked sialyl residues, as well as atypical alpha2,8-linked sialyl residues. Additionally, at least one of their antenna was terminated with an oligo/polysialyl unit, similar to recombinant Kv3.1 and N-CAM. In contrast, brain Kv1 glycoproteins consisted of sialyl residues with alpha2,8-linkage, as well as sialyl residues linked to internal carbohydrate residues of the carbohydrate chains of the N-glycans. This type of linkage was also supported for Kv3 glycoproteins. To date, such sialyl linkage has only been identified in gangliosides, not N-linked glycoproteins. We conclude that all six Kv channels contribute to the atypical sialylated N-glycan pool in mammalian brain. Identification of these novel sialylated N-glycan structures implicate a connection between potassium channel activity and atypical sialylated N-glycans in modulating and fine tuning the excitable properties of neurons in the nervous system.
PMID: 18937645 [PubMed - as supplied by publisher]