Cell Bio: Week 10

What influences which signals a cell detects and how strongly it responds?

The types and amounts of receptors a cell expresses.

What are the two distinct steps that can be tested separately in cell signaling?

Signal binding and receptor activation, and the cellular response.

What does acetylcholine activate in heart pacemaker cells?

A GPCR, promoting GDP-GTP exchange on the Gα subunit of Gi.

What allows Gα to rejoin Gβγ and ends ion-channel activation?

GTP hydrolysis.

What happens if GTP hydrolysis is delayed?

The signaling response is prolonged.

What does Gα hydrolysis of GTP to GDP do?

Switches Gα off.

What happens if Gα fails to hydrolyze GTP?

Adenylyl cyclase activation and cAMP production are prolonged.

What enzyme terminates the cAMP signal?

cAMP phosphodiesterase.

What does cAMP phosphodiesterase do?

Hydrolyzes cAMP into AMP.

What determines the strength and duration of cAMP signaling?

Both cAMP production and breakdown.

What fur color results when Gα cannot hydrolyze GTP to GDP?

Dark brown fur.

Why does a Gα mutation that prevents GTP hydrolysis cause dark brown fur?

Gα cannot switch itself off, causing prolonged cAMP production and pigment signaling.

What does nitric oxide (NO) activate in neighboring smooth muscle cells?

Guanylyl cyclase.

What does guanylyl cyclase convert GTP into?

cGMP.

What promotes smooth muscle relaxation?

NO activating guanylyl cyclase, which produces cGMP.

What determines cGMP levels?

Production by guanylyl cyclase and breakdown by cGMP phosphodiesterase.

What happens when unphosphorylated Bad binds Bcl2?

It inhibits Bcl2, a protein that normally suppresses apoptosis.

What does activated Akt do to Bad?

Phosphorylates Bad, inactivating it and releasing active Bcl2.

What is the result of activated Akt releasing active Bcl2?

Promotion of cell survival.

What do both GPCRs and RTKs activate that leads to Ca2+ release?

Phospholipase C.

What does Ca2+ release lead to?

Calmodulin activation and activation of CaM-kinase.

How can different receptor pathways integrate multiple signals?

They activate shared downstream proteins and transcriptional regulators.

What does constitutively active Ras do?

Signals without activation by an upstream protein.

If constitutively active Ras restores signaling when protein X is inactive, where is X?

Upstream of Ras.

If signaling still requires protein Y when Ras is constitutively active, where is Y?

Downstream of Ras.

In the pathway RTK → X → Ras → Y → response, what happens if a required downstream step is blocked?

Signaling stops even when Ras remains active.

What must organ-chip validation establish?

Human biological relevance by showing that the model reproduces the biology needed for its intended application.

What must studies demonstrate to validate organ chips?

Predictive accuracy against appropriate human reference data and reproducibility across repeated experiments and, where appropriate, laboratories.

What must organ chips demonstrate for commercial and regulatory adoption?

Validated, reproducible performance for a clearly defined intended use, such as predicting drug-induced liver injury.

What does organ-chip validation require?

Repeated testing across devices, experiments, and laboratories to establish reliable predictions of relevant human responses.