Neurotrophic and Growth Factors: Hedgehog, Notch, and Cytoskeleton Signaling

Vocabulary practice covering the signaling pathways of Hedgehog and Notch, as well as the dynamics and regulation of the actin and microtubule cytoskeleton.

NIH Overall Impact Score

A 9-point scoring scale ranging from 1 (exceptional) to 9 (poor) that evaluates the significance and likelihood for a project to exert a sustained, powerful influence on the research field.

Vertebrate Hedgehog (Hh) Subgroups

The three subgroups of Hedgehog ligands found in vertebrate systems: Desert Hedgehog (Dhh), Indian Hedgehog (Ihh), and Sonic Hedgehog (Shh).

Sonic Hedgehog (Shh)

The most broadly expressed Hh ligand in embryos and adults, critical for cell fate determination in embryonic and adult neural progenitor cells.

Hedgehog (Hh) Modifications

Post-translational processes including self-cleavage, cholesterol modification, and palmitoylation that make Hh a 'sticky' molecule adhering to the plasma membrane.

Primary Cilia

Microtubule-based sensory organelles found on most human cells that transmit extracellular signals into intracellular biochemical responses; defects lead to diseases known as ciliopathies.

PTCH (Patched)

A receptor that, in the absence of Hedgehog, catalytically inhibits SMO and prevents signaling.

SMO (Smoothened)

A protein that is inhibited by PTCH; when Hh is present, SMO becomes phosphorylated, its degradation is blocked, and it interacts with Cos2 to activate downstream signaling.

Gli (Gli2 and Gli3)

Downstream transcriptional factors of the Hh pathway; they function as repressors when proteolytically truncated (facilitated by PKA, GSK3b, and CKI) and as activators when preserved in full length.

Cyclopamine

A Hedgehog signaling inhibitor derived from the Meadow Corn lily that works by inactivating SMO.

Basal Cell Carcinoma

A type of cancer associated with the inactivation of Patched, which leading to an increase in Hh signaling.

Notch Ligands

The short-range signaling molecules Delta and Jagged (or Serred in Drosophila) that bind to Notch receptors.

NICD (Notch Intracellular Domain)

The fragment of the Notch receptor released by $\gamma$-secretase cleavage that translocates to the nucleus to activate target genes.

Fringe Family

A group of glycosyltransferases that control the glycosylation of Notch, dictating which Delta ligand the receptor will bound and activated by.

Lateral Inhibition

A process where a cell with higher Delta levels (such as a Sensory Organ Precursor) inhibits neighboring cells from adopting the same fate via Notch signaling.

Numb

A cell-fate determinant protein that is asymmetrically distributed during cell division to regulate Notch signaling in daughter cells.

Three Major Cytoskeleton Networks

Actin filaments ($7\,nm$), Intermediate filaments ($10\,nm$), and Microtubules ($25\,nm$).

G-actin and F-actin

G-actin refers to the globular monomer, while F-actin refers to the polarized helical polymer formed upon assembly, depending on ATP hydrolysis.

Actin Treadmilling

A steady state where the mass of filaments remains constant because the rate of subunit addition at the plus end ($CC(+) = 0.2\,\mu M$) equals the rate of loss at the minus end ($CC(-) = 2.0\,\mu M$).

Arp2/3 Complex

A protein complex that acts as a nucleation site for actin filaments, often creating branched networks.

RhoGTPases

A family of signaling proteins (including Rho, Rac, and Cdc42) that stimulate actin nucleation and organization into structures like stress fibers, lamellipodia, and filopodia.

GEF (Guanine Nucleotide Exchange Factor)

A regulator that stimulates the exchange of GDP for GTP to activate small GTPases.

GAP (GTPase Activating Protein)

A negative regulator that stimulates GTP hydrolysis, inactivating small GTPases.

GDI (GDP Dissociation Inhibitor)

A protein that inhibits the release of GDP and helps cycle GTPases between the cytoplasm and the membrane.

PAK (p21-activated kinase)

A family of kinase effectors for Rac and Cdc42 that regulate cytoskeleton dynamics, cell motility, and synaptic plasticity.

Cofilin

An actin-binding enzyme that severs F-actin filaments; its activity is regulated by phosphorylation, primarily being inactivated by LIMK and activated by SSH1.

Microtubules

Rigid, hollow tubes of $25\,nm$ diameter made of $\alpha$-tubulin and $\beta$-tubulin heterodimers that assemble into 13 polarized protofilaments using GTP hydrolysis.