Premium
The p38 mitogen‐activated protein kinase pathway negatively regulates Ca 2+ ‐activated K + channel trafficking in developing parasympathetic neurons
Author(s) -
Chae KwonSeok,
Dryer Stuart E.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03201.x
Subject(s) - microbiology and biotechnology , biology , protein kinase a , actin , phosphorylation , p38 mitogen activated protein kinases , chemistry
Abstract The trafficking of large‐conductance Ca 2+ ‐activated K + channels (K Ca ) in chick ciliary ganglion neurons is regulated by growth factors. Here we show that a canonical p38 cascade inhibits K Ca 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 K Ca 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 K Ca , whereas stabilization of F‐actin inhibited the effect of SB202190 on K Ca trafficking. SB202190 also caused an immunochemically detectable increase in K Ca on the plasma membrane. Inhibition of p38 decreased the extent of cortical F‐actin in ciliary neurons. Macroscopic K Ca 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 K Ca , 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 K Ca .