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The ER’s extensive network of membrane sheets and tubules provides…
approximately 20-30 times more surface area than the plasma membrane in a mammalian cell
The nuclear envelope is thought to have arisen from…
plasma membrane infoldings surrounding the DNA, which also contributed to the development of the endomembrane system
An exposed nuclear localization signal (NLS) allows…
a protein to be recognized by a cytosolic nuclear import receptor
Regulatory binding partners can…
retain proteins in the cytosol by masking their NLS or anchoring them
Cellular signals can…
release restraint and permit nuclear import
The outward secretory pathway moves…
proteind and lipids from the ER through the Golgi apparatus to the plasma membrane or lysosomes
The inward endocytic pathway transports…
extracellular material from the plasma membrane through early and late endosomes to lysosomes
A transport vesicle can carry…
multiple types of cargo, while selective sorting gives its membrane a composition that differs from its source membrane
Targeting proteins direct each vesicle to…
the appropriate type of target membrane, helping preserve organelle identity
The Golgi apparatus consists of…
stacks of 3-20 flattened membrane sacs called cisternae
Proteins and lipids enter at the…
ER-facing cis Golgi network and exit from the trans Golgi network
Glycosylation begins in the ER, where…
a core oligosaccharide is attached (enzymes in successive Golgi compartments then modify its sugar composition)
Protein modification and sorting processing follows the route:
ER → cis Golgi → central Golgi → trans Golgi (blocking early step can prevent later sugar additions)
During exocytosis, a secretory vesicle’s membrane…
fuses with the plasma membrane, releasing soluble cargo outside the cell and adding its membrane to the cell surface
Cholesterol travels through the bloodstream in…
low-density lipoprotein (LDL) particles that bind LDL receptors on target cells
Endosomal acidification normally seperates…
LDL from its receptor, allowing the receptor to recycle while LDL proceeds towards lysosomes
Preventing LDL-receptor dissociation can…
disrupt normal sorting and reduce efficient delivery of LDL cholesterol for release and cellular use
Centrifugation seperates…
free proteins from proteins that co-sediment with organelles
Co-sedimentation alone cannot…
distinguish proteins inside an organelle from those attached to its surface
An intact organelle membrane protects…
imported soluble proteins from external protease, while surface-exposed proteins are digested
Detergent disrupts the membrane…
allowing protease to digest previously protected proteins in the organelle lumen
The types and amounts of receptors a cell expresses influence…
which signals it detects and how strongly it responds
Signal binding, receptor activation, and cellular response are…
distinct steps that can tested seperately
In heart pacemaker cells…
acetylcholine activates a GPCR, promoting GDP-GTP exchange on the Ga subunit of G_i
GTP hydrolysis allows…
Ga to rejoin Gby and ends channel activation (delaying this step prolongs the response)
Ga hydrolyzes…
GTP to GDP to switch itself off
Failure to hydrolyze GTP prolongs…
adenylyl cyclase activation and cAMP production
cAMP phosphodiesterase terminates…
the signal by hydrolyzing cAMP productionT
The strength and duration of cAMP signaling depends on…
both cAMP production and breakdown, influencing downstream cellular responses
NO enters neighboring smooth muscle cells and…
activates guanylyl cyclase, which converts GTP into cGMP to promote relaxation
cGMP levels depend on its…
production by guanylyl cyclase and breakdown by cGMP phosphodiesterase
Unphosphorylated Bad binds and inhibits…
BCl2, a protein that normally suppresses apoptosis
Activated Akit phosphorylates…
Bad, inactivating it and releasing active BCl2 to promote cell survival
Both GPCRs and RTKs can activate…
phospholipase C, leading to Ca2+ release, calmodulin activation, and activation of CaM-kinase
Different receptor pathways can activate…
shared downstream proteins and transcriptional regulators, allowing cells to integrate multiple signals
Constitutively active Ras…
signals without activation by and upstream protein. If it restores signaling when protein X is inactive, X acts upstream of Ras
If signaling still requires protein Y when Ras is constitutively active…
Y acts downstream of Ras
The process of making cell mutation:
RTK → X → Ras → Y → response, blocking a required downstream step can stop signaling even when Ras remains active
Validation must establish human biological relevance by showing that…
the model reproduces the biology needed for its intended application
Studies must demonstrate predictive accuracy against…
appropriate human reference data and reproducibility across repeated experiments and, where appropriate, laboratories
Organ chips must demonstrate…
validated, reproducible performance for a clearly defined intended use, such as predicting drug-induced liver injury
Validation requires repeated testing across…
devices, experiments, and laboratories to establish reliable predictions of relevant human responses
Similar rod domains and assembly patterns produce…
filaments with a similar diameter of approximately 10 nm
Two dimers assemble into a…
staggered, antiparallel tetramer
Tetramers associate side by side, and successive bundles…
overlap and interleave as the filament elongates
Numerous noncovalent interactions across overlapping regions…
distribute tension, producing a strong, flexible filament
Keratin intermediate filaments form…
strong, flexible networks inside epithelial cells that resist stretching and mechanical stress
Desmosomes anchor…
keratin networks at cell-cell contacts, allowing neighboring cells to share mechanical forces
Hemidesmosomes anchor…
keratin networks to the underlying basal lamina, helping secure the epithelial sheet
Dynamic instability allows…
microtubules to switch between growth and rapid shrinkage
Free tubulin dimers…
exchange GDP for GTP
Reduced GTP-tubulin avaliability…
slows subunit addition, making cap loss and rapid shrinkage more likely
Ca2+ binding to troponin…
shifts tropomyosin, exposing the sites needed for myosin attachment and contraction
Without Ca2+ binding to troponin…
tropomyosin continues to restrict myosin access, even when Ca2+ and ATP are avaliable
Fibroblasts attach to…
secreted collagen and exert traction, pulling and compacting fibrils into organized sheets or cables
Collagen forms…
extracellular fibrils that provide tensile strength
Fibronectin is an…
extracellular adhesive protein that links collagen to integrins
Integrins span the…
plasma membrane and connect to intracellular actin filaments through adaptor proteins
Proteoglycans consist of…
a core protein with attached GAG chains, often forming a bottlebrush-like structure
Cartilage contains…
abundant proteoglycans within a collagen network, creating a resilient matrix that resists compression
Aggrecan, a cartilage proteoglycan, binds to…
hyaluronan through link proteins to form large extracellular aggregates
Negatively charged GAGs attract…
cations and draw in water, creating a hydrated gel that resists compression and cushions tissues
The apical surface faces a…
lumen or the external enviroment
Cell junctions connect…
neighboring epithelial cells and help maintain the sheet’s organization and barrier function
The basal lamina is a…
thin extracellular matrix layer beneath the epithelium, composed mainly of type IV collagen and laminin
Underlying connective tissue provides…
structural support and often contains blood vessels that supply the epithelium
Tight junctions seal…
neighboring epithelial cells and restrict water-soluble molecules from passing through intercellular spaces
Transmembrane claudins and occludins form…
branching sealing strands between adjacent plasma membranes