cellular mechanism of intrinsic plasticity
mediated by changes of ion channels in the membrane (channel diversity and abundancy
biophysical properties
expression level (global
gene diversity
transcriptional regulation
alternative splicing
posttranslational modification
subcellular localization
regulatory sequences
components
TF binding sites
transcription factors
activator
often assemble into complexes
coactivator
corepressor
repressor
mechanism
masking activation surface
direct interaction with the general TFs
activators work synergistically
competitive binding with activator
enhancer
silencer
recruitment of chromatin remodeling complexes
promoter
epigenetics mechanism
epigenetics
inheritable without changing DNA sequence
mechanism
histone modification (acetylation/methylation)
chromatin relaxed with modification
methylation of cytosine
chromatin relaxed without methylation
enhance transcription
enhance transcription
produce the different forms of protein from the same gene
e.g. Nav1.5/1.6: presence or absence of exon 18
translational control
miRNA
types
phosphorylation
glycosylation
acetylation
ubiquitination
SUMOylation (small ubiquitin-like modifier)
affect
activity
translocation
interaction
affect ion channel activity
regulating ion channel stability and trafficking
tagging lysine
PY motif in ion channels can be ubiquitinated lead to different tissue distribution
e.g.
localization of voltage gated ion channels in axons
uneven distribution of ion channels in neuron
pathology
epilepsy
affect
ion channels
techniques
genome-wide analysis
targeted gene analysis
micro-array analysis
expression
qPCR
promoter analysis
transcription factor analysis
bioinformatics analysis
use reporter gene ( in vivo or in vitro
cloning sequences
same process as promoter analysis
analyze functional effect on target protein