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