Atypical sialylated N-glycan structures are attached to neuronal voltage-gated potassium channels

2009 ◽  
Vol 29 (5) ◽  
pp. 301-313 ◽  
Author(s):  
Tara A. Cartwright ◽  
Ruth A. Schwalbe
Keyword(s):  
Potassium Channels ◽  
Neuroblastoma Cells ◽  
Fine Tuning ◽  
Mammalian Brain ◽  
Migration Patterns ◽  
Voltage Gated ◽  
Adult Rat ◽  
Electrophoretic Migration ◽  
Kv Channels ◽  
Rat Brain Membranes

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 with those of NCAM (neural cell adhesion molecule), transferrin and the Kv3.1 protein heterologously expressed in B35 neuroblastoma cells. Metabolic labelling of the carbohydrates combined with glycosidase digestion reactions were utilized to show that the N-glycan of recombinant Kv3.1 protein was capped with an oligo/poly-sialyl unit. All three brain Kv3 glycoproteins, like NCAM, were terminated with α2,3-linked sialyl residues, as well as atypical α2,8-linked sialyl residues. Additionally, at least one of their antennae was terminated with an oligo/poly-sialyl unit, similar to recombinant Kv3.1 and NCAM. In contrast, brain Kv1 glycoproteins consisted of sialyl residues with α2,8-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 a sialyl linkage has only been identified in gangliosides, not N-linked glycoproteins. We conclude that all six Kv channels (voltage-gated K+ channels) contribute to the α2,8-linked sialylated N-glycan pool in mammalian brain and furthermore that their N-glycan structures contain branched sialyl residues. Identification of these novel and unique 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.

Novel Kv3 glycoforms differentially expressed in adult mammalian brain contain sialylated N-glycans

2008 ◽  
Vol 86 (1) ◽  
pp. 21-30 ◽  
Author(s):  
Ruth A. Schwalbe ◽  
Melissa J. Corey ◽  
Tara A. Cartwright
Keyword(s):  
Spinal Cord ◽  
Central Nervous System ◽  
Nervous System ◽  
The Other ◽  
Mammalian Brain ◽  
Migration Patterns ◽  
Voltage Gated ◽  
Adult Rat ◽  
The Central Nervous System ◽  
Adult Mammalian Brain

The N-glycan pool of mammalian brain contains remarkably high levels of sialylated N-glycans. This study provides the first evidence that voltage-gated K+ channels Kv3.1, Kv3.3, and Kv3.4, possess distinct sialylated N-glycan structures throughout the central nervous system of the adult rat. Electrophoretic migration patterns of Kv3.1, Kv3.3, and Kv3.4 glycoproteins from spinal cord, hypothalamus, thalamus, cerebral cortex, hippocampus, and cerebellum membranes digested with glycosidases were used to identify the various glycoforms. Differences in the migration of Kv3 proteins were attributed to the desialylated N-glycans. Expression levels of the Kv3 proteins were highest in cerebellum, whereas those of Kv3.1 and Kv3.3 were much lower in the other 5 regions. The lowest level of Kv3.1 was expressed in the hypothalamus, whereas the lowest levels of Kv3.3 were expressed in both thalamus and hypothalamus. The other regions expressed intermediate levels of Kv3.3, with spinal cord expressing the highest. The expression level of Kv3.4 in the hippocampus was slightly lower than that in cerebellum, and was closely followed by the other 4 regions, with spinal cord expressing the lowest level. We suggest that novel Kv3 glycoforms may endow differences in channel function and expression among regions throughout the central nervous system.

[125I]Margatoxin, an Extraordinarily High Affinity Ligand for Voltage-Gated Potassium Channels in Mammalian Brain

Biochemistry ◽  
1995 ◽  
Vol 34 (41) ◽  
pp. 13627-13634 ◽  
Author(s):  
Hans-Guenther Knaus ◽  
Robert O. A. Koch ◽  
Andreas Eberhart ◽  
Gregory J. Kaczorowski ◽  
Maria L. Garcia ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Mammalian Brain ◽  
Voltage Gated ◽  
High Affinity ◽  
Affinity Ligand ◽  
High Affinity Ligand

scholarly journals Molecular basis of functional diversity of voltage-gated potassium channels in mammalian brain.

1989 ◽  
Vol 8 (11) ◽  
pp. 3235-3244 ◽  
Author(s):  
W. Stühmer ◽  
J.P. Ruppersberg ◽  
K.H. Schröter ◽  
B. Sakmann ◽  
M. Stocker ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Functional Diversity ◽  
Molecular Basis ◽  
Mammalian Brain ◽  
Voltage Gated

scholarly journals The Amyloid Precursor Protein C99 Fragment Modulates Voltage-Gated Potassium Channels.

2021 ◽  
Vol 55 (S3) ◽  
pp. 157-170
Keyword(s):  
Amyloid Precursor Protein ◽  
Protein Interactions ◽  
Precursor Protein ◽  
Xenopus Laevis Oocytes ◽  
Cellular Functions ◽  
Voltage Gated ◽  
Adult Rat ◽  
Kv Channel ◽  
Kv Channels

BACKGROUND/AIMS: The Amyloid Precursor Protein (APP) is involved in the regulation of multiple cellular functions via protein-protein interactions and has been most studied with respect to Alzheimer's disease (AD). Abnormal processing of the single transmembrane-spanning C99 fragment of APP contributes to the formation of amyloid plaques, which are causally related to AD. Pathological C99 accumulation is thought to associate with early cognitive defects in AD. Here, unexpectedly, sequence analysis revealed that C99 exhibits 24% sequence identity with the KCNE1 voltage-gated potassium (Kv) channel β subunit, comparable to the identity between KCNE1 and KCNE2-5 (21-30%). This suggested the possibility of C99 regulating Kv channels. METHODS: We quantified the effects of C99 on Kv channel function, using electrophysiological analysis of subunits expressed in Xenopus laevis oocytes, biochemical and immunofluorescence techniques. RESULTS: C99 isoform-selectively inhibited (by 30-80%) activity of a range of Kv channels. Among the KCNQ (Kv7) family, C99 isoform-selectively inhibited, shifted the voltage dependence and/or slowed activation of KCNQ2, KCNQ3, KCNQ2/3 and KCNQ5, with no effects on KCNQ1, KCNQ1-KCNE1 or KCNQ4. C99/APP co-localized with KCNQ2 and KCNQ3 in adult rat sciatic nerve nodes of Ranvier. Both C99 and full-length APP co-immunoprecipitated with KCNQ2 in vitro, yet unlike C99, APP only weakly affected KCNQ2/3 activity. Finally, C99 altered the effects on KCNQ2/3 function of inhibitors tetraethylammounium and XE991, but not openers retigabine and ICA27243.

scholarly journals Modeling of the Binding of Peptide Blockers to Voltage-Gated Potassium Channels: Approaches and Evidence

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 35-46 ◽  
Author(s):  
V. N. Novoseletsky ◽  
A. D. Volyntseva ◽  
K. V. Shaitan ◽  
M. P. Kirpichnikov ◽  
A. V. Feofanov
Keyword(s):  
Potassium Channels ◽  
Rational Design ◽  
Computational Simulation ◽  
Bound State ◽  
Amino Acid Residues ◽  
Molecular Tools ◽  
Computational Approaches ◽  
Functional Roles ◽  
Voltage Gated ◽  
Kv Channels

Modeling of the structure of voltage-gated potassium (KV) channels bound to peptide blockers aims to identify the key amino acid residues dictating affinity and provide insights into the toxin-channel interface. Computational approaches open up possibilities for in silico rational design of selective blockers, new molecular tools to study the cellular distribution and functional roles of potassium channels. It is anticipated that optimized blockers will advance the development of drugs that reduce over activation of potassium channels and attenuate the associated malfunction. Starting with an overview of the recent advances in computational simulation strategies to predict the bound state orientations of peptide pore blockers relative to KV-channels, we go on to review algorithms for the analysis of intermolecular interactions, and then take a look at the results of their application.

Gene transcription of brain voltage-gated potassium channels is reversibly regulated by oxygen supply

2003 ◽  
Vol 285 (6) ◽  
pp. R1317-R1321 ◽  
Author(s):  
Howard M. Prentice ◽  
Sarah L. Milton ◽  
Daniela Scheurle ◽  
Peter L. Lutz
Keyword(s):  
Potassium Channels ◽  
Oxygen Supply ◽  
Brain Activity ◽  
Acute Hypoxia ◽  
Mrna Levels ◽  
Voltage Gated ◽  
Kv Channel ◽  
Kv Channels ◽  
Voltage Dependent ◽  
Channel Expression

Voltage-dependent potassium channels (Kv channels) are important determinants of brain electrical activity. Hypoxia may be an important modifier, because several voltage-gated K+ channels are reversibly blocked by acute hypoxia and are thought to act as oxygen sensors. Here we show, using the anoxia-tolerant turtle brain ( Trachemys scripta) as a model, that brain Kv1 channel transcription is reversibly regulated by oxygen supply. We found that in turtle brains exposed to 4-h anoxia Kv1 transcripts were reduced to 18.5% of normoxic levels. Kv1 channel mRNA levels were restored to normal within 4 h of subsequent reoxygenation. Our results provide clear evidence that brain Kv channel expression is sensitive to oxygen supply and indicate an important mechanism that matches brain activity to oxygen supply.

scholarly journals Characterization of a Novel Radiolabeled Peptide Selective for a Subpopulation of Voltage-gated Potassium Channels in Mammalian Brain

2001 ◽  
Vol 277 (6) ◽  
pp. 3886-3893 ◽  
Author(s):  
Judith Racapé ◽  
Alain Lecoq ◽  
Régine Romi-Lebrun ◽  
Jessica Liu ◽  
Martin Kohler ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Mammalian Brain ◽  
Voltage Gated
Sign in / Sign up

Export Citation Format

Share Document