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What are the four essential components of a signaling pathway
Signal molecule, receptor, intracellular signaling molecules, and effectors
What are the five main types of signaling based on distance?
Contact-dependent, paracrine, autocrine, synaptic, and endocrine
What is contact-dependent signaling?
A signaling mechanism where the signal molecule remains bound to the surface of the signaling cell and affects only target cells in direct physical contact.
(Used in development and immune responses.)
What is paracrine signaling?
A local signaling mechanism where the signal molecule is secreted and acts on nearby target cells within the same tissue.
(Common in growth factors and local mediators.)
What is autocrine signaling?
A form of signaling in which cells respond to signaling molecules that they themselves secrete.
(Often seen in immune cells and during development.)
What is synaptic signaling?
Long-distance signaling where neurotransmitters are released from a neuron’s axon terminal and travel across a synapse to reach a specific target cell.
(Occurs rapidly and with high specificity between neurons or between neurons and muscle cells.)
What is endocrine signaling?
A long-range signaling mechanism where hormones are secreted into the bloodstream and act on distant target cells throughout the body.
(Used in hormonal regulation such as insulin or adrenaline.)
Which type of signal uses cell-surface receptors?
Hydrophilic signals that cannot cross the membrane.
Which type of signal uses intracellular receptors?
Hydrophobic signals that can cross the plasma membrane.
Why can different cells respond differently to the same signal?
They have different receptors or intracellular signaling pathways.
What are the three main classes of receptor proteins?
Ion-channel linked, G-protein linked, and enzyme-linked receptors.
What are two major types of molecular switches in signaling?
Phosphorylation/dephosphorylation and GTP-binding switches.
What is the role of scaffold proteins?
They organize signaling proteins together to increase speed and specificity.
What are modular binding domains used for?
They allow signaling proteins to interact through specific recognition sites.
Why do some cellular responses require integration of multiple signals?
To ensure the response fits the cell’s state and environment.
What determines whether a signaling response is fast or slow?
Fast responses modify existing proteins; slow responses require new gene expression.
What is the difference between graded and switch-like responses?
Graded responses increase gradually; switch-like responses occur abruptly once a threshold is reached.
What is positive feedback?
It amplifies a signaling response, sometimes making it self-sustaining.
What is negative feedback?
It inhibits or dampens a signaling response.
How can cells desensitize to extracellular signals?
By internalizing or degrading receptors, or activating inhibitory pathways.
What structural feature defines GPCRs?
They are 7-pass transmembrane proteins.
How do GPCRs activate G proteins?
Ligand binding causes Gα to exchange GDP for GTP and dissociate from Gβγ.
What do both Gα and Gβγ subunits do once activated?
They relay messages to downstream targets.
What enzyme synthesizes cyclic AMP (cAMP)?
Adenylyl cyclase.
Which Gα subunit increases cAMP?
Gas
How does cAMP act inside the cell?
It activates protein kinase A (PKA), which then activates CREB to regulate gene expression.
What enzyme degrades cAMP?
Phosphodiesterase
What enzyme does Gαq activate?
Phospholipase C-β (PLC-β)
What are the products of PLC-β activity?
IP₃ and DAG
What is the role of IP₃ and DAG?
IP₃ releases Ca²⁺ from the ER; Ca²⁺ and DAG activate protein kinase C (PKC)
How are GPCR signals downregulated?
GPCR kinases phosphorylate the receptor, and arrestin binds to target it for endocytosis
What happens when Gα is activated in Dictyostelium?
It stimulates adenylyl cyclase, increasing cAMP secretion to signal nearby cells
What does Gβγ activate in Dictyostelium signaling?
PI3 kinase, which produces PIP₃ for actin recruitment during cell movement.
What effect do activating mutations in Gα have?
They prevent proper cell migration.
How do olfactory receptors signal?
Through cAMP, which opens ion channels and depolarizes neurons.
What is rhodopsin and where is it found?
A GPCR in rod photoreceptors used for dim-light vision.
What happens to rhodopsin when it absorbs light?
11-cis retinal converts to all-trans retinal, activating the receptor.
What G protein is used in phototransduction?
Transducin (Gαt).
What enzyme does transducin activate?
cGMP phosphodiesterase
What is the effect of reduced cGMP levels?
Closure of cGMP-gated Na⁺ channels, leading to membrane hyperpolarization
How are RTKs activated?
Ligand binding causes dimerization and autophosphorylation
What do phosphorylated tyrosines on RTKs do?
They serve as docking sites for downstream signaling proteins
Which monomeric G protein is activated by RTKs?
Ras
What pathway does Ras activate?
The MAP kinase (MAPK) cascade
What is the sequence of kinases in the MAPK pathway?
MAPKKK → MAPKK → MAPK
What are the main outcomes of MAPK activation?
Protein phosphorylation and gene expression changes
How does Akt promote survival and growth?
By interacting with mTOR complexes — mTORC1 for growth and mTORC2 for survival
What is the role of Notch signaling?
It controls cell fate via contact-dependent signaling during development.
How is the Notch receptor activated?
By proteolytic cleavage after binding to the Delta ligand on a neighboring cell.
What is the JAK-STAT pathway activated by?
Cytokines binding to enzyme-associated receptors that recruit JAK kinases.
What happens to STATs after activation?
They are phosphorylated, dimerize, and move to the nucleus to regulate transcription.
What kind of receptors mediate TGFβ signaling?
Serine/threonine kinase receptors.
What are Smads?
Transcription factors activated by TGFβ receptors that form complexes to change gene expression
How do nuclear hormone receptors regulate transcription?
Ligand binding releases inhibitory proteins and recruits coactivators to initiate gene transcription
What are the three main cytoskeletal filament types?
What are the three main cytoskeletal filament types?
What does actin control?
Cell shape and cell fission during division.
What are microtubules responsible for?
Mitotic spindle formation and movement of cilia and flagella.
What is the role of intermediate filaments?
Providing mechanical strength in cell-cell junctions.
How do cytoskeletal filaments remain dynamic?
By continuous assembly and disassembly.
What gives actin filaments polarity?
The asymmetric shape of actin monomers bound to ATP
What are the three phases of actin polymerization?
Nucleation (lag), elongation (rapid growth), and steady state (equilibrium)
Which end of actin filaments is more dynamic?
The plus (+) end
What is treadmilling?
Addition of subunits at the plus end and loss at the minus end, keeping length constant
When does treadmilling occur?
When the total monomer concentration is between Cc(T) and Cc(D).
What proteins nucleate actin filaments?
Formin (plus end) and Arp2/3 (minus end, branching).
What are thymosin and profilin?
Thymosin inhibits actin assembly; profilin promotes assembly.
What do tropomodulin and capping proteins do?
Tropomodulin caps the minus end; capping proteins cap the plus end.
What is cofilin’s function?
Accelerates filament disassembly
What do filamin, fimbrin, and α-actinin do?
Cross-link actin filaments into bundles or networks.
What does spectrin do?
Links actin filaments to the plasma membrane.
What direction does myosin move along actin?
Toward the plus (+) end.
What triggers skeletal muscle contraction?
Ca²⁺ release from the sarcoplasmic reticulum after an action potential
What is the role of troponin and tropomyosin in contraction?
Ca²⁺ binds troponin, shifting tropomyosin to expose myosin-binding sites on actin
How do myosin filaments generate movement?
By ATP-driven power strokes that slide actin filaments past each other
What are microtubules made of?
α- and β-tubulin heterodimers forming 13 protofilaments
What is dynamic instability?
Alternating growth and shrinkage of microtubules due to GTP cap loss or gain
What is catastrophe vs. rescue?
Catastrophe = rapid depolymerization; Rescue = regaining a GTP cap and growth
What is the role of the γ-tubulin ring complex (γ-TuRC)?
Nucleates microtubule growth at the minus end
What is the centrosome?
The primary microtubule-organizing center (MTOC) in animal cells
What does stathmin do?
Binds tubulin dimers and prevents polymerization.
What does kinesin-13 do?
Promotes microtubule disassembly
What does katanin do
Severs microtubules
What are MAPs and XMAP215?
MAPs stabilize microtubules; XMAP215 promotes growth
What is the difference between tau and MAP2?
Tau creates tightly packed bundles; MAP2 allows wider spacing.
What direction do kinesins move?
Toward the plus (+) end of microtubules
What direction do dyneins move?
Toward the minus (–) end
What are the two main types of dynein?
Axonemal (cilia/flagella) and cytoplasmic (vesicle transport)
What organisms contain intermediate filaments?
Only some metazoans (e.g., vertebrates, nematodes, mollusks)
What is the basic structure of intermediate filaments?
Coiled-coil dimers forming staggered, antiparallel tetramers.
What are key properties of intermediate filaments?
Flexible, easy to bend, hard to break
What are keratins?
A diverse family of intermediate filaments providing strength to hair, skin, and nails.