PMID: 16847056

 

    Legend: Gene, Sites

Title : Isoform-specific effects of the beta2 subunit on voltage-gated sodium channel gating

Abstract :

1. Voltage-gated sodium channels ( Nav ) are complex glycoproteins comprised of an alpha subunit and often one to several beta subunits
2. We have shown that sialic acid residues linked to Nav alpha and beta1 subunits alter channel gating
3. To determine whether beta2-linked sialic acids similarly impact Nav gating, we co-expressed beta2 with Nav1 .5 or Nav1 .2 in Pro5 (complete sialylation) and in Lec2 (essentially no sialylation) cells
4. Beta2 sialic acids caused a significant hyperpolarizing shift in Nav1 .5 voltage-dependent gating, thus describing for the first time an effect of beta2 on Nav1 .5 gating
5. In contrast, beta2 caused a sialic acid-independent depolarizing shift in Nav1 .2 gating
6. A deglycosylated mutant, beta(2-DeltaN), had no effect on Nav1 .5 gating, indicating further the impact of beta2 N-linked sialic acids on Nav1 .5 gating
7. Conversely, beta(2-DeltaN) modulated Nav1 .2 gating virtually identically to beta2 , confirming that beta2 N-linked sugars have no impact on Nav1 .2 gating
8. Thus, beta2 modulates Nav gating through multiple mechanisms possibly determined by the associated alpha subunit
9. Beta1 and beta2 were expressed together with Nav1 .5 or Nav1 .2 in Pro5 and Lec2 cells
10. Together beta1 and beta2 produced a significantly larger sialic acid-dependent hyperpolarizing shift in Nav1 .5 gating
11. Under fully sialylating conditions, the Nav1 .2
12. beta1. beta2 complex behaved like Nav1 .2 alone
13. When sialylation was reduced, only the sialic acid-independent depolarizing effects of beta2 on Nav1 .2 gating were apparent
14. Thus, the varied effects of beta1 and beta2 on Nav1 .5 and Nav1 .2 gating are apparently synergistic and highlight the complex manner, through subunit- and sugar-dependent mechanisms, by which Nav activity is modulated

Output (sent_index, trigger, protein, sugar, site):

• 1. glycoproteins, , channels, -, -
• 1. glycoproteins, , glycoproteins, -, -
• 13. beta2, , beta2, only the sialic acid-independent depolarizing effects, -
• 2. linked, , Nav alpha, sialic acid residues, -
• 2. linked, , beta1, sialic acid residues, -
• 3. beta2, , beta2, Lec2 (essentially no sialylation) cells, -
• 3. beta2, , beta2, complete sialylation, -
• 3. beta2, , beta2, essentially no sialylation, -

Output(Part-Of) (sent_index, protein, site):

• 3. beta2, Pro5

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX