BMS5208: Cell Signalling III - Gene Expression and Membrane Permeability

Flashcards covering steroid hormone classification, receptor domain structures (including Zinc fingers and SREs), mechanisms of gene expression regulation (HATs/HDACs), and the complex intracellular Ca2+ signalling system.

Progestagens

A major class of steroid hormones responsible for the maintenance of pregnancy.

Mineralocorticoids

A major class of steroid hormones that function to increase blood volume and pressure.

Glucocorticoids

A major class of steroid hormones that promote high blood glucose.

(O)Estrogens

A major class of steroid hormones involved in the development of secondary sexual characteristics.

Androgens

A major class of steroid hormones involved in the development of secondary sexual characteristics.

Zinc-finger domain

The second domain of a steroid hormone receptor needed for DNA binding to a steroid response element (SRE) with high affinity ($Kd \sim 1\,nM$).

Zinc Finger structural motif

A DNA-binding domain sequence represented as $\text{Cys-X-X-Cys-X(13)–Cys–X-X-Cys}$, rich in basic amino acids like $Cys$, $Arg$, and $Lys$.

Steroid Response Elements (SREs)

Labels within the DNA sequence identifying genes as targets for transcription factors, consisting of two 'half sites' that bind the Zn finger domains of a receptor dimer.

Palindromic SRE

A DNA sequence (e.g., $TGTTCT \dots TCTTGT$) where a receptor homodimer binds head-to-head, typical for true steroid hormones.

Direct Repeat SRE

A DNA sequence (e.g., $TGACCT \dots TGACCT$) where a receptor heterodimer binds head-to-tail, typical for thyroid hormone, Vitamin D, and retinoids.

Histone Acetylases (HATs)

Proteins recruited by steroid hormone receptors to unravel chromosomes by acetylating histones, thereby promoting gene expression.

Histone Deacetylases (HDACs)

Proteins removed from chromosomes by steroid hormone receptors to facilitate the initiation or enhancement of transcription.

NRAMP channels

Channels that transport $Fe^{2+}$ (a co-factor for proteins like haem) across the plasma membrane.

GLUT4

A transporter molecule that moves glucose into cells in response to changes in membrane permeability.

Excitation-contraction coupling

A signal transduction process in the heart where nervous stimulation leads to muscle contraction, discovered by Ringer in 1883.

Stimulus-secretion coupling

A signal transduction process in the pancreas where hormonal stimulation leads to enzyme secretion, discovered by Hermann in 1932.

Hydroxyapatite

The mineral form of calcium consisting of crystals of insoluble calcium phosphate laid onto a collagen-rich matrix.

PMCA pump

A plasma membrane $Ca^{2+}$-ATPase responsible for the expulsion of calcium from the cell to restore cytoplasmic levels.

SERCA pump

A pump located in the ER membrane used to remove $Ca^{2+}$ from the cytoplasm via sequestration into internal stores.

IP3 (Inositol trisphosphate)

A second messenger generated from the cleavage of $PIP_2$ by phospholipase C that acts as a ligand to release $Ca^{2+}$ from the endoplasmic reticulum.

Capacitative Ca2+ Entry (CCE)

A biphasic signalling mechanism where the depletion of $ER$ calcium stores triggers an influx of extracellular calcium to support sustained responses.

STIM1

An $ER$ protein that migrates to the plasma membrane when $ER$ $Ca^{2+}$ levels decrease to interact with $Orai1$ and $TrpC$ proteins.

Calcium Release-Activated Channel (CRAC)

A plasma membrane channel formed by $Orai1$ and $TrpC$ proteins that opens in response to the migration of $STIM1$.

FURA-2

A fluorescent indicator dye used with confocal microscopy to image and quantify cytosolic $Ca^{2+}$ concentrations.