Amino Acid Properties of Trafficking Determinants in the Outer Pore-Forming Region of Kv1 Potassium Channels in Cell Lines.

Different classes of Kv1 potassium channels have different trafficking patterns despite having very similar amino acid sequences. Two amino acids responsible for these differences have been identified in the outer pore turret region of Kv1.1 and Kv1.

The degree of N-glycosylation affects the trafficking and cell surface expression levels of Kv1.4 potassium channels.

Kv1.4 potassium channels are heavily glycosylated proteins involved in shaping action potentials and in neuronal excitability and plasticity. Kv1.

The Kv1.3 potassium channel is localized to the cis-Golgi and Kv1.6 is localized to the endoplasmic reticulum in rat astrocytes.

The functions of voltage-gated potassium (Kv) channels in neurons have been well defined, whereas their roles in glial cells are not fully understood. Kv1.1, Kv1.

Spinocerebellar ataxia-13 Kv3.3 potassium channels: arginine-to-histidine mutations affect both functional and protein expression on the cell surface.

The voltage-gated potassium channel Kv3.3 is the causative gene of SCA13 (spinocerebellar ataxia type 13), an autosomal dominant neurological disorder. The four dominant mutations identified to date cause Kv3.

N-glycosylation promotes the cell surface expression of Kv1.3 potassium channels.

The voltage-gated potassium channel Kv1.3 plays an essential role in modulating membrane excitability in many cell types. Kv1.

Characterization of the Kv1.1 I262T and S342I mutations associated with episodic ataxia 1 with distinct phenotypes.

Episodic ataxia type 1 (EA-1) is an autosomal dominant neurological disorder caused by mutations in the potassium channel Kv1.1. Two EA-1 mutations, I262T and S342I, have been identified with unique clinical phenotypes, but their functional and biochemical properties have not been fully investigated.

DmSAS is required for sialic acid biosynthesis in cultured Drosophila third instar larvae CNS neurons.

Sialylation is an important carbohydrate modification of glycoconjugates that has been shown to modulate many cellular/molecular interactions in vertebrates. In Drosophila melanogaster (Dm), using sequence homology, several enzymes of the sialylation pathway have been cloned and their function tested in expression systems. Here we investigated whether sialic acid incorporation in cultured Dm central nervous system (CNS) neurons required endogenously expressed Dm sialic acid synthase (DmSAS).

The Kv1.2 potassium channel: the position of an N-glycan on the extracellular linkers affects its protein expression and function.

Voltage-gated potassium Kv1 channels have three extracellular linkers, the S1-S2, the S3-S4, and the S5-P. The S1-S2 is the only linker that has an N-glycan and it is at a conserved position on this linker on Kv1.1-Kv1.

Kv1 potassium channel C-terminus constant HRETE region: arginine substitution affects surface protein level and conductance level of subfamily members differentially.

We have shown previously that truncating all of the variable cytoplasmic C-terminus of Kv1.1 potassium channels to G421stop had only a small inhibitory effect on their cell surface conductance density levels and cell surface protein levels. Here we investigated the role of a highly conserved cytoplasmic C-terminal charged region of five amino acids (HRETE) of the S6 transmembrane domain in the protein and conductance expression of Kv1.

The glycosylation state of Kv1.2 potassium channels affects trafficking, gating, and simulated action potentials.

We presented evidence previously that decreasing the glycosylation state of the Kv1.1 potassium channel modified its gating by a combined surface potential and a cooperative subunit interaction mechanism and these effects modified simulated action potentials. Here we continued to test the hypothesis that glycosylation affects channel function in a predictable fashion by increasing and decreasing the glycosylation state of Kv1.

Effects of Kv1.1 channel glycosylation on C-type inactivation and simulated action potentials.

Kv1.1 channels are brain glycoproteins that play an important role in repolarization of action potentials. In previous work, we showed that lack of N-glycosylation, particularly lack of sialylation, of Kv1.

Amino acids in the pore region of Kv1 potassium channels dictate cell-surface protein levels: a possible trafficking code in the Kv1 subfamily.

Kv1.1 and Kv1.4 potassium channels have different pore region determinants that were found to affect their cell-surface levels positively and negatively [Zhu, Watanabe, Gomez and Thornhill (2001) J.

Glycosylation affects the protein stability and cell surface expression of Kv1.4 but Not Kv1.1 potassium channels. A pore region determinant dictates the effect of glycosylation on trafficking.

Kv1.1 and Kv1.4 potassium channels are plasma membrane glycoproteins involved in action potential repolarization.

Allowed N-glycosylation sites on the Kv1.2 potassium channel S1-S2 linker: implications for linker secondary structure and the glycosylation effect on channel function.

N-glycosylation is a post-translational modification that plays a role in the trafficking and/or function of some membrane proteins. We have shown previously that N-glycosylation affected the function of some Kv1 voltage-gated potassium (K+) channels [Watanabe, Wang, Sutachan, Zhu, Recio-Pinto and Thornhill (2003) J. Physiol.

Trafficking of Kv1.4 potassium channels: interdependence of a pore region determinant and a cytoplasmic C-terminal VXXSL determinant in regulating cell-surface trafficking.

Kv1.4 and Kv1.1 potassium channel homomers have been shown to exhibit different intracellular trafficking programmes and cell-surface expression levels in cell lines: a determinant in the pore region of Kv1.

The permeation and activation properties of brain sodium channels change during development.

BTX-modified sodium channels from 15-day embryonic (E15) rat forebrains were studied in planar lipid bilayers. Compared to postnatal sodium channels, E15 channels had a lower maximal single channel conductance, whereas their permeation pathway sensed a comparable surface charge density and had a similar apparent binding affinity for sodium ions. The steady-state activation curve of E15 channels was significantly more hyperpolarized and had a shallower slope than postnatal channels.

Glycosylation affects rat Kv1.1 potassium channel gating by a combined surface potential and cooperative subunit interaction mechanism.

The effect of glycosylation on Kv1.l potassium channel function was investigated in mammalian cells stably transfected with Kv1.l or Kv1.

Heteromeric Kv1 potassium channel expression: amino acid determinants involved in processing and trafficking to the cell surface.

Kv1.4 and Kv1.1 potassium channels are expressed in brain as mature glycoproteins that are trans-Golgi glycosylated.