Molecular Signaling within Neurons

This set of vocabulary flashcards covers molecular signaling within neurons, including G protein cycles, GPCR pathways, and the structure and function of kinases and phosphatases.

GTPase activating protein (GAP)

A protein, such as an RGS protein, that functions in conjunction with GEFs for small G protein (GTP/GDP) exchange and stimulates the inactivation of G proteins.

$G_{\alpha}$ subunit

The subunit of a heterotrimeric G protein that binds to GDP in its inactive state and GTP in its active state.

Heterotrimeric G proteins

Also known as large G proteins, these are partners of GPCRs consisting of three subunits: $\alpha$, $\beta$, and $\gamma$.

Monomeric G proteins

Also known as small G proteins (e.g., Ras), which change between GTP-bound (active) and GDP-bound (inactive) conformations.

Guanine nucleotide exchange factor (GEF)

A protein that facilitates the exchange of GDP for GTP to activate G proteins.

$G_{\beta\gamma}$ subunits

The complex of G protein subunits that dissociates from the $G_{\alpha}$ subunit upon GTP binding and can directly gate nearby ion channels, such as inhibiting presynaptic calcium channels.

$G_s$ GPCR pathway

A signaling pathway where Norepinephrine binds to $\beta$-adrenergic receptors, activating Adenylyl cyclase to increase cAMP and Protein kinase A (PKA), leading to increased protein phosphorylation.

$G_i$ GPCR pathway

A signaling pathway where Dopamine binds to $D2$ receptors, inhibiting Adenylyl cyclase to decrease cAMP and Protein kinase A (PKA), leading to decreased protein phosphorylation.

$G_q$ GPCR pathway

A signaling pathway where Glutamate binds to mGluR, activating Phospholipase C to produce Diacylglycerol and $IP_3$, leading to $Ca^{2+}$ release and Protein kinase C activation.

Calcium ($Ca^{2+}$)

A second messenger that binds to sensor proteins like Calmodulin and Synaptotagmin and modulates storage channels in the ER/SR.

Kinases

Enzymes that put phosphate groups onto amino acids; major classes include Serine/Threonine (activated by GPCRs) and Tyrosine (enzyme-linked receptors).

Catalytic domain

The essential domain of a kinase molecule that contains the ATP and substrate binding domains.

Autoinhibitory domain

A domain within a kinase that blocks the catalytic domain until an activator or second messenger binds to cause a conformational change.

Protein Kinase A (PKA)

A kinase that is activated when cAMP binds to its regulatory subunits, causing the release of active catalytic domains to phosphorylate substrates.

CaMKII

A protein kinase holoenzyme made of 14 subunits that is activated by the binding of $Ca^{2+}/\text{Calmodulin}$ to its regulatory domain.

Phosphatases

Enzymes that dephosphorylate proteins by removing phosphate groups, opposing the action of kinases.

Calcineurin (PP2B)

A major type of phosphatase in neurons that is sensitive to calcium and activated by calmodulin, playing an important role in learning and LTD.