Biol 4004 - Exam 2 Flashcards

Intracellular Organization and Protein Sorting, Intracellular Membrane Traffic, Cell Signaling, and Cytoskeleton I (weeks 5 - 8)

Actin filament and microtubule assembly where the concentration of free subunits determines the growth rate of these filaments.

Polymerize (polymerization)

Rate of addition of new subunits to the filament ends exactly balances the rate of subunit dissociation.

Critical concentration (Cc)

Protein that helps regulate the distance between adjacent microtubules. Forms bundles of stable microtubules that are closely packed together. Also forms large aggregates in neurons called neurofibrillary tangles.

Tau

Promotes microtubule elongation. Binds tubulin subunits and delivers them to the (+) ends of microtubules.

XMAP215

Family of motor proteins that bind microtubules and move towards the (-) ends of microtubules.

Dyneins

Process by which microtubules are constantly switching between rapid growth and rapid shrinkage.

Dynamic instability

The rate limiting step in filament formation. Spontaneous assembly of a few subunits is unstable until the initial oligomer is stabilized by multiple subunit-subunit contacts; then elongation is rapid afterwards.

Nucleation

A dense spherical matrix recruited by the centrioles where microtubule nucleation occurs.

Pericentriolar material

Soluble subunits of microtubules. Are composed of GTP-bound ⍺ and proteins.

Tubulin dimers

Protein that binds to tubulin subunits and prevents their addition to microtubules. Sequesters free tubulin dimers and maintains the pool of active subunits near the critical concentration.

Stathmin

Proteins that bind to microtubules to regulate the length, stability, number and geometry of microtubules.

Microtubule-associated proteins (MAPs)

A single long, whip-like protrusion whose undulations propel a cell through a fluid. In eukaryotic cells, these are a longer version of cilia.

Flagella

Process by which filaments remain the same length overall due to addition of subunits at the (+) end at the same rate as loss of subunits at the (-) end.

Treadmilling

Superfamily of motor proteins that almost all move towards the (+) ends of microtubules (one exception)

Kinesins

A bundle of microtubules (9 outer doublet microtubules and 2 central single microtubules) that forms the core of both cilia and flagella and is responsible for their movement.

Axonemes

Sites that are rich in γTuRC. In most animal cells, these are located near the cell nucleus.

Microtubule-organizing centers (MTOCs)

An initial oligomer of subunits that is stabilized by subunit-subunit interactions.

Nucleus

Proteins that bind to the (+) ends of microtubules and increase the rate of microtubule depolymerization.

Catastrophe factors

Dynein-mediated movement of cargo towards the (-) end of microtubules.

Centripetal movement

A short cylindrical array of microtubules; similar to a basal body. In animal cells, they are found as a pair in the center of a centrosome.

Centrioles

Process by which all cilia and flagella grow from basal bodies.

Intraflagellar transport

Rapid elongation of microtubules due to regaining their GTP-cap.

Rescue

Actin filament and microtubule disassembly where the rate of subunit loss is constant.

Depolymerize (depolymerization)

Composed of monomer proteins organized into a ring-shaped structure with other associated proteins. After nucleation, it remains bound to the (-) end of the microtubule preventing subunit gain or loss.

γ-tubulin ring complexes (γTuRC)

Tightly attached to axonemes by their tails to the A tubule. Their motor heads make transient ATP-dependent attachments to the B tubule of the adjacent doublet.

Dynein arms

Kinesin mediated movement of cargo towards the (+) end of microtubules.

Centrifugal movement

Found on the apical surface of some epithelial cells. Beat in a whip-like motion to either propel a single cell through fluid or to move fluid across the epithelial cell surface.

Cilia

Found at regular intervals along the axoneme and help to attach adjacent microtubule doublets.

Nexin links

A large protein complex that associates with cytoplasmic dynein in order to efficiently transport most organelles

Dynactin

Primary microtubule-organizing center in animal cells and acts as the spindle pole during mitosis. Contains a pair of centrioles.

Centrosome

Human diseases linked to defects in motile and primary cilia.

Ciliopathies

Protein that severs microtubules near the centrosome.

Katanin

Plasma membrane associated structures that anchor flagella, motile cilia and nonmotile cilia to the cell surface. The core of these structures contains a single centriole with 9 groups of fused microtubule triplets arranged in a cartwheel.

Basal bodies

Proteins that bind to the (+) or (-) end, respectively, and prevent gain or loss of subunits from the filament.

Capping proteins

Most cells contain 1 of these structures that are non-motile and located on its cell surface. It acts as a mechanical and sensory receptor, but is non-motile due to a lack of dynein arms.

Primary cilia

Rapid shrinkage of microtubules due to loss of the GTP-cap due to nucleotide hydrolysis

Catastrophe

Protein that helps regulate the distance between adjacent microtubules. Forms bundles of stable microtubules that are widely spaced apart.

MAP2

Trafficking of vesicles or organelles along axonal microtubules from cell body to axon terminal carried out by kinesins

Anterograde movement

The longitudinal arrangements of subunits, which run the length of the filament. Linear strings of subunits joined end to end to provide strength and adaptability to actin filaments and microtubules.

Protofilaments

A triphosphate subunit on the plus end of a filament that stabilizes the filament and promotes elongation.

GTP cap/ATP cap

Trafficking of vesicles or organelles along axonal microtubules from axon terminal to cell body carried out by dyneins.

Retrograde movement

Hedgehog pathway

Components of this signaling pathway are held in close proximity due to their localization in the primary cilium.

Receptor tyrosine kinase (RTK)

Transmembrane proteins with encoded or associated kinase activity; ligand binding induces dimerization that brings the kinase domains together to activate them.

Src homology 2 (SH2) domains

Sequence in an intracellular signaling protein that binds to phosphotyrosines on the cytosolic tail of a receptor.

PI 3-kinase

The enzyme that phosphorylates inositol phospholipids at the 3 carbon position in the inositol ring head group.

Autocrine signaling

When a cell responds to a signal it produces because it expresses the receptor

Paracrine signaling

Short-range, limited diffusion of a signal molecule affects nearby cells that express the receptor.

SMADs

Latent transcriptional regulatory proteins activated by transforming growth factor-β (TGFβ) signaling.

Pleckstrin homology (PH) domains

Protein domain used by intracellular signaling proteins to dock at PIP3 in the membrane.

Protein Kinase C

A kinase that is activated by increased Ca2+

Phospholipase C- (PLC-)

Acts on the phosphoinositide PI(4,5,)2 to produce IP3 (inositol 1,3,5-trisphosphate) and diacylglycerol.

Wnt pathway

This signaling pathway triggers dissociation of the "destruction complex", stabilizing -catenin which transfers to the nucleus where it regulates transcription.

Calmodulin

A Ca2+ binding protein without enzymatic activity that activates target proteins (including kinases) to produce a cellular response to increased cytosolic Ca2+

Ras

A small, plasma membrane-anchored GTPase that uses the adaptor protein Grb2 to respond to receptor tyrosine kinase activation.

JAK-STAT

Cytokine receptors are associated with this kinase and transcription factor that transmit their intracellular signal

Heterotrimeric G protein

Has ⍺, β, and γ subunits, ⍺ and γ are membrane anchored. Binding of a receptor (GEF) triggers activation and dissociation of G⍺ (GTPase) from Gβγ.

Ca2+-Calmodulin Kinase II (CaMKII)

Has twelve individual kinase domains with inactive and "popped" active conformations that allow this complex to serve as a ratcheting frequency detector.

Guanalyl cyclase

Converts GTP to cGMP in response to photoactivation of the GPCR rhodopsin.

Mitogen activated protein (MAP) Kinase cascade

A series of kinases that relay and amplify the signal from Ras, ending by phosphorylating effector proteins

Ɣ-secretase

Performs the third, intracellular cleavage of the Notch receptor, releasing the cytoplasmic tail to act as a transcription factor.

G protein coupled receptor (GPCR)

Seven pass transmembrane receptor proteins that bind and regulate membrane anchored heterotrimeric G proteins that transmit the signal.

CREB

A protein phosphorylated by Protein Kinase A (PKA) that binds to DNA elements and activates transcription in response to cAMP.

Src homology 3 (SH3) domains

Proline-rich motifs that allow intracellular proteins to interact, typically found in adaptor proteins

Endocrine signaling

Signals secreted into the bloodstream are circulated throughout the body, any cell with a receptor responds

Phosphatase

The type of enzyme that removes phosphate groups.

Diacylglycerol

A simple lipid produced by Phospholipase C that remains in the membrane; activates Protein Kinase C when it binds along with Ca2+

TGF signaling

Local mediators including activin that bind single-pass transmembrane receptors with serine/threonine kinase activity, phosphorylate Smads.

Scaffold

A protein that binds other proteins that work together in series, like kinases, facilitating their sequential use and reducing cross-talk between pathways.

Adenylyl cyclase

A membrane associated enzyme that converts ATP to the second messenger cAMP.

Protein Kinase A (PKA)

Most of the effects of cAMP are mediated by activating this kinase that phosphorylates target proteins like CREB.

Kinase

The type of enzyme that adds phosphate groups.

Notch pathway

Contact-dependent signaling. The ligand and receptor are transmembrane proteins; upon activation, the receptor is processed to produce a transcription factor.

Effector proteins

The targets at the end of signaling pathways that implement an appropriate cellular change.

Phosphatidylinositol phosphates (PIPs)

Phophoinositides that are variably phosphorylated on carbons 3, 4, and 5 of the inositol head group.

Gq

Activates PLC-β

Gs

Activates adenylyl cyclase

Gi

Inhibits adenylyl cyclase

G-olf

Activates adenylyl cyclase in olfactory sensory neurons

Gt

Activates cyclic GMP phosphodiesterase in rod photoreceptors

Coat-recruitment GTPases

A family of proteins that inserts into the membrane and binds coat proteins and cargo during COPI-, COPII-, and retromer-coated vesicle formation; includes Sar1

COPI-coated vesicles

Coated vesicles that transport material from the Golgi back to the ER

Dynamin

Forms a spiral around the neck of a clathrin-coated bud, regulates membrane fusion, vesicle release

Autophagy

"Self eating", when a cell engulfs components of its own cytoplasm for degradation in lysosomes

ESCRTs

Protein complexes that regulate membrane budding including intralumenal vesicle formation and cytokinesis

Rab

A family of small GTPases; controls vesicular traffic by recruiting effector proteins that define membrane identity and function, mediate vesicular docking and fusion

Clathrin-coated vesicles

Coated vesicles that transport material endocytosed at the plasma membrane and within endosomal compartments

Cis face of the Golgi

Side of the Golgi stack at which material enters

Golgi reassembly and stacking proteins (GRASPs)

Structural proteins that create a scaffold between adjacent cisternae to form the Golgi stacks

SNAREs

Mediate vesicle docking and fusion to specific target membranes by winding into stable 4-helix complexes

Lysosomes

Membrane-bound organelle which contains digestive enzymes most active at low pH

Macropinocytosis

"Cell drinking", when a cell non-specifically traps extracellular fluid and material

Phosphoinositides (PIPs)

Variable phosphorylation of the 3', 4', and 5' position of this phosphilipid's sugar head group recruits different proteins to create functionally distinct membrane domains

ER exit sites

COPII-coated vesicles bud from this specialized region of the ER that is devoid of ribosomes

Mannose-6-phosphate (M6P)

This modification identifies acid (lysosome) hydrolases, formed by trimming GlcNAc from N-linked glycosylation

Complexin

Binds to SNAREs to prevent them from fully assembling, holds the complex in a frozen, "primed" metastable state

Receptor-mediated endocytosis

Clathrin complexes with a transmembrane receptor at the plasma membrane during this process

Cis Golgi Network (CGN)

This part of the Golgi includes fused vesicular clusters that arrive from the ER containing proteins and lipids that need sorting and processing

Endocytosis

General term for taking material into the cell through invagination and internalization of the plasma membrane

KDEL

The sequence that recruits soluble ER resident proteins into COPI retrieval vesicles for recycling back to the ER

Trans face of the Golgi

Side of the Golgi stack at which material exits