Abstract
The trafficking of large-conductance Ca2+-activated K + channels (KCa) in chick ciliary ganglion neurons is regulated by growth factors. Here we show that a canonical p38 cascade inhibits KCa trafficking in ciliary ganglion neurons. Two different p38 inhibitors (SB202190 or SB203580) or over-expression of dominant-negative forms of several components of the p38 cascade increased KCa in ciliary neurons. Inhibition of protein synthesis or Golgi processing had no effect on this phenomenon, suggesting that p38 is acting at a distal step of the trafficking pathway. Depolymerization of filamentous actin (F-actin) increased functional expression of KCa, whereas stabilization of F-actin inhibited the effect of SB202190 on KCa trafficking. SB202190 also caused an immunochemically detectable increase in KCa on the plasma membrane. Inhibition of p38 decreased the extent of cortical F-actin in ciliary neurons. Macroscopic KCa is suppressed by transforming growth factor (TGF) β3. Application of TGFβ3 increased the phosphorylation of p38 in ciliary neurons and increased cortical F-actin. Thus, the p38 signaling cascade endogenously suppresses development of functional KCa, in part by stabilizing an F-actin barrier that prevents plasma membrane insertion of functional channel complexes. This cascade also appears to mediate inhibitory effects of TGFβ3 on the expression of KCa.
Original language | English |
---|---|
Pages (from-to) | 367-379 |
Number of pages | 13 |
Journal | Journal of Neurochemistry |
Volume | 94 |
Issue number | 2 |
DOIs | |
State | Published - Jul 2005 |
Keywords
- Actin barrier
- BK channel
- Slowpoke
- Trafficking
- Transforming growth factor β3
- p38 mitogen-activated protein kinase