Cell Biology: Protein Sorting, the Mitotic Spindle, and Cell Cycle Control

Comprehensive vocabulary review flashcards covering nuclear and mitochondrial protein translocation, mitotic spindle dynamics and chromosome segregation, extracellular growth and survival signaling, and intracellular cell-cycle checkpoint regulation.

Protein Sorting

The biological process of directing and transporting proteins synthesized in the cytosol to their designated cellular compartments or organelles.

Gated Transport

The mechanism that mediates bidirectional traffic of proteins and RNA between the cytosol and the nucleus through nuclear pore complexes.

Transmembrane Transport

The translocation of proteins across a membrane bilayer directly into an organelle, specifically occurring in the endoplasmic reticulum and mitochondria.

Vesicular Transport

The transport of proteins from one membrane-enclosed compartment to another using membrane-bound transport vesicles along the secretory pathway.

Signal Sequence

A continuous, contiguous stretch of amino acids at the terminal end of a protein that serves as an address label to direct the protein to a specific destination.

Signal Patch

A sorting signal composed of internal amino acid residues from distant regions of the linear polypeptide sequence that come together only after the protein folds.

Nuclear Pore Complex (NPC)

An octagonal macromolecular channel perforating the nuclear envelope, composed of nucleoporins, that mediates passive diffusion of small molecules and selective active transport of folded macromolecules.

Nuclear Localization Signal (NLS)

A peptide sequence or surface patch on a cargo protein recognized by nuclear import receptors to initiate transport into the nucleus.

Ran GTPase

A monomeric GTPase that acts as a molecular switch to impart directionality to nuclear import and export based on a compartmentalized gradient of Ran-GDP in the cytosol and Ran-GTP in the nucleus.

Ran-GAP (GTPase-Activating Protein)

A cytosolic regulatory protein that induces Ran to hydrolyze its bound GTP to GDP and inorganic phosphate, maintaining high cytosolic Ran-GDP levels.

Ran-GEF (Guanine Nucleotide Exchange Factor)

A chromatin-bound nuclear protein that stimulates Ran to release GDP and bind GTP, maintaining high nuclear Ran-GTP concentrations.

Mitochondrial Signal Sequence

An N-terminal amino acid sequence that folds into an amphipathic $\alpha$-helix with positively charged amino acids on one side and uncharged nonpolar amino acids on the other.

TOM Complex

The Translocase of the Outer Mitochondrial Membrane, consisting of receptor proteins (TOM 20, TOM 5) and a channel-forming pore (TOM 40), required for translocating all nuclear-encoded mitochondrial precursor proteins across the outer membrane.

TIM 23 Complex

The Translocase of the Inner Mitochondrial Membrane that transports proteins across into the mitochondrial matrix and mediates the insertion of specific transmembrane proteins into the inner membrane.

TIM 22 Complex

An inner mitochondrial membrane translocase specialized for mediating the insertion of multipass carrier proteins into the inner mitochondrial membrane.

OXA Complex

A protein translocator complex located in the inner mitochondrial membrane that mediates the insertion of inner membrane proteins synthesized inside the mitochondrial matrix or redirected from the matrix space.

Cross-Bridge Ratchet Model

A translocation mechanism where mitochondrial Hsp70 bound to TIM 23 undergoes ATP-driven conformational changes that actively pull the polypeptide chain into the mitochondrial matrix.

Matrix Processing Peptidase (MPP)

A mitochondrial matrix protease that cleaves the N-terminal mitochondrial signal sequence from imported precursor proteins following translocation across the inner membrane.

Astral Microtubules

Spindle microtubules that radiate outward from centrosomes toward the cell cortex, orienting the spindle and positioning the spindle poles within the dividing cell.

Kinetochore Microtubules

Microtubules of the mitotic spindle whose plus ends attach end-on to the kinetochores of condensed sister chromatids to mediate their alignment and poleward segregation.

Overlap Microtubules

Microtubules from opposite spindle poles that interdigitate at the spindle equator and interact with multimeric motor proteins to slide apart and stabilize the bipolar spindle architecture.

Kinesin-5 (BimC)

A plus-end-directed, homotetrameric motor protein that cross-links antiparallel overlap microtubules and slides them past one another to push centrosomes apart during spindle assembly and anaphase B.

Kinesin-14

A minus-end-directed multimeric motor protein that cross-links adjacent microtubules to pull minus ends together and focus the spindle poles.

Condensin

A five-subunit protein complex with coiled-coil ATP- and DNA-binding domains that utilizes ATP hydrolysis to coil DNA and condense chromosomes during prophase, activated by M-Cdk phosphorylation.

Cohesin

A ring-shaped protein complex that holds replicated sister chromatids together from S phase onward, most of which is replaced along chromosome arms by condensin during prophase.

Ndc80 Complex

A rod-like protein complex at the outer kinetochore that directly binds along the lattice of the microtubule plus end, maintaining attachment while permitting polymerization and depolymerization.

CENP-E (Centromere-Associated Protein E)

A plus-end-directed kinesin motor protein located in the fibrous corona of the outer kinetochore that assists in capturing microtubules and aligning chromosomes at the metaphase plate.

Chromokinesin (Kid)

A plus-end-directed motor protein located on chromosome arms that exerts the polar ejection force (astral ejection force), pushing chromosome arms away from the poles toward the spindle equator.

Poleward Flux

The steady treadmilling of tubulin subunits toward spindle poles at metaphase, characterized by net tubulin subunit addition at microtubule plus ends and net depolymerization at minus ends.

Anaphase A

The mitotic stage during which daughter chromosomes move poleward as a result of the shortening of kinetochore microtubules driven by depolymerization at their plus and minus ends.

Dam1 Ring

A ring-shaped protein complex found in yeast kinetochores that encircles the microtubule and couples the energy of protofilament curling during microtubule depolymerization to poleward chromosome movement.

Anaphase B

The mitotic stage during which spindle poles are pushed and pulled further apart through the combined action of plus-end-directed motors on overlap microtubules and dynein motors anchored to the cell cortex pulling on astral microtubules.

Total Cell Mass

The cumulative volume and mass of an organ or organism, determined by total cell number (the rate of cell division minus cell death) and individual cell growth.

Growth Factors

Extracellular signaling proteins that stimulate an increase in individual cell size by promoting macromolecular synthesis (primarily protein synthesis) and inhibiting macromolecular degradation.

Receptor Tyrosine Kinase (RTK)

An enzyme-linked cell surface receptor whose ligand-induced dimerization activates intrinsic kinase activity, triggering cross-phosphorylation of tyrosine residues on its cytoplasmic domains.

PI 3-Kinase Pathway

An intracellular pathway activated by growth factor receptors in which PI 3-kinase phosphorylates $\text{PI(4,5)P}_2$ to form $\text{PI(3,4,5)P}_3$, subsequently activating TOR and S6K to phosphorylate ribosomal protein S6 and stimulate translation.

Nerve Growth Factor (NGF)

A neurotrophic signaling protein discovered by Rita Levi-Montalcini that promotes the survival and axonal outgrowth of responsive neurons via TrkA receptor tyrosine kinase signaling.

Mitogens

Extracellular signaling molecules, such as PDGF and EGF, that stimulate cell division by activating intracellular cascades that overcome molecular brakes blocking entry into the cell cycle.

Restriction Point

The critical checkpoint in late $G_1$ phase where vertebrate cells commit to entering S phase in the presence of extracellular mitogens, or withdraw into a quiescent $G_0$ state in their absence.

Myc

An immediate early gene-regulatory protein transcribed downstream of the Ras-MAP kinase pathway that drives transcription of cyclin D, SCF subunits, and E2F to promote S-phase entry.

Retinoblastoma Protein (Rb)

A tumor suppressor protein that acts as an inhibitor of cell-cycle progression by binding and inhibiting E2F until it is phosphorylated and inactivated by $G_1\text{-Cdk}$ and $G_1\text{/S-Cdk}$.

p19ARF

A tumor suppressor protein induced by abnormally high levels of Myc that binds Mdm2, preventing Mdm2 from degrading p53 and thereby causing cell-cycle arrest or apoptosis to protect against oncogenic transformation.

Survival Factors

Extracellular signal molecules that suppress apoptosis, typically by activating Protein Kinase B (PKB) to phosphorylate and inactivate the pro-apoptotic protein Bad, freeing Bcl-2 to inhibit cell death.

Cyclin-Dependent Kinases (Cdks)

A family of serine/threonine protein kinases that control cell-cycle progression, whose catalytic activities depend on association with cyclins and fluctuate rhythmically throughout the cell cycle.

Cyclin-Activating Kinase (CAK)

A kinase that fully activates a Cdk by phosphorylating a specific threonine residue on its T-loop, rearranging the loop to expose the active catalytic site.

Wee1 Kinase

A protein kinase that introduces an inhibitory phosphate onto Cdk (such as Cdk1 of M-Cdk), suppressing its enzymatic activity until the phosphate is removed.

Cdc25 Phosphatase

A phosphatase that removes inhibitory phosphate groups placed by Wee1 on Cdks, rapidly activating M-Cdk and triggering entry into mitosis.

p27

A Cdk inhibitor protein (CKI) that binds to and physically distorts active cyclin-Cdk complexes (such as $G_1\text{/S-Cdk}$ and $\text{S-Cdk}$), preventing kinase activity during $G_1$.

SCF Complex

A multi-protein ubiquitin ligase that targets phosphorylated CKI proteins (such as p27) and $G_1\text{/S-cyclins}$ for polyubiquitylation and proteasomal degradation, maintaining constant activity across the cell cycle.

Anaphase-Promoting Complex / Cyclosome (APC/C)

A ubiquitin ligase that initiates sister chromatid separation at anaphase by targeting securin for degradation and drives exit from mitosis by targeting M-cyclin for destruction in the proteasome.

APC-Cdc20

The active APC/C complex formed upon binding Cdc20 during early mitosis that ubiquitinates securin to trigger anaphase and initiates the degradation of M-cyclin.

APC-Cdh1

The active APC/C complex formed in late mitosis upon association with Cdh1 that keeps M-cyclin levels low throughout telophase and $G_1$ to ensure proper exit from mitosis.

Securin

An inhibitory chaperone protein that binds and suppresses separase activity until anaphase onset, when its ubiquitylation by APC/C leads to its destruction in the proteasome.

Separase

An endopeptidase that cleaves the cohesin rings linking sister chromatids together, triggering chromosome separation once relieved of securin inhibition at anaphase.

Spindle Attachment Checkpoint (SAC)

A cell-cycle checkpoint that arrests cells at the metaphase-to-anaphase transition when unattached kinetochores recruit Mad2, which binds and inhibits Cdc20-APC/C activation.

p53

A gene regulatory protein and tumor suppressor that is stabilized following DNA damage to stimulate transcription of the CKI p21, blocking cell-cycle progression into S phase.

p21

A Cdk inhibitor protein (CKI) transcribed in response to active p53 that binds and inactivates $G_1\text{/S-Cdk}$ and $\text{S-Cdk}$ complexes, preventing entry into S phase following DNA damage.