#cell motility

Cytoskeleton

In cilia, what keeps the doublet microtubules from sliding past each other completely?

Motile cilia contain nine plus two axoneme where outer doublets composed of A and B tubules slide relative to each other when axonemal dynein arms anchored on A tubule bind and walk toward minus end of neighboring B tubule, activated in coordinated wave from base to tip. Unrestrained sliding would cause doublets to telescopically extend apart, disrupting structure. Restraint provided by nexin links now recognized as nexin-dynein regulatory complex, elastic proteinaceous bridges composed of DRC1-4 and associated proteins connecting adjacent doublets circumferentially every ninety six nanometers. They limit sliding amplitude to about sixty to seventy nanometers per beat cycle and store elastic energy that recoils to produce bending. Additional resistance from radial spokes transmitting signals from central pair regulates dynein activity. Electron tomography shows N-DRC as hook-like structures. Protease digestion generating sliding disintegration assay causes ATP-induced complete doublet separation, confirming structural role. Kinesin does not reside in axoneme, actin absent, phosphorylation tunes waveform not tethering.

Ref: Porter & Sale J Cell Biol; nexin-DRC elastic links limit sliding, convert sliding to ciliary bending.

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Cytoskeleton

How does Myosin I differ from Myosin II?

Myosin superfamily diversified into eighteen classes sharing conserved motor domain but divergent tail architectures dictating cargo and filament forming ability defining cellular specialization. Myosin II forms bipolar thick filaments through antiparallel association of long coiled coil tails each filament containing hundreds of molecules with heads at both ends ideal for sliding antiparallel actin during sarcomere contraction and cytokinetic ring constriction where force needed. In contrast myosin I is monomeric single headed myosin with short tail lacking coiled coil filament forming propensity. Instead its TH1 domain enriched in basic residues binds directly to acidic phosphoinositide containing membranes allowing crosslinking actin to membrane generating tension. Tail homology domains also bind adaptors for vesicle transport during endocytosis and exocytosis tensioning microvilli and stereocilia adaptation in auditory hair cells. Thus myosin I functions as membrane actin tether and vesicle transporter whereas myosin II acts as contractile filament builder illustrating how tail evolution switches mechanical output from transport to contraction.

Ref: Alberts et al., Molecular Biology of the Cell, Chapter 16 – Myosin I single headed transporter vs Myosin II bipolar filaments.

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Cytoskeleton

Which of the following proteins is required for the formation of lamellipodia?

Lamellipodium broad veil like extension 1 to 5 micron wide 0.1 to 0.2 micron thick driving mesenchymal migration requires continuous branched actin assembly at leading edge. Key organizer is Rac1 GTP small GTPase activating pentameric WAVE regulatory complex comprising WAVE, Abi, Nap1, Sra1 and HSPC300. Upon activation Rac1 binding to Sra1 releases VCA domain of WAVE which binds G actin and Arp2/3 complex at membrane, inducing nucleation of daughter filaments at 70 degree angle. Iterative branching creates dense network with barbed ends abutting membrane, polymerizing and generating pushing force essential for protrusion. Imaging with photoactivatable actin shows retrograde flow balancing polymerization. Pharmacological inhibition CK666 blocking Arp2/3 activation site abrogates lamellipodia formation, cells instead form filopodia via formins, confirming Arp2/3 indispensability for lamellipodia. Myosin II provides retraction at rear, dynein microtubule motor for centrosome positioning, spectrin supporting membrane cortex, while Arp2/3 specifically drives lamellipodia protrusive network and motility. Continuous turnover of branched meshwork allows rapid adaptation to chemotactic cues and directional persistence during migration.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 16: Lamellipodia Formation and Arp2/3 Requirement.

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Cytoskeleton

What is the main function of the Arp2/3 complex?

Branched actin organization essential for protrusion relies on Arp2/3 complex discovering daughter filaments on sides of mother filaments. Complex comprises Arp2, Arp3 actin related proteins plus ARPC1 to ARPC5 subunits forming 220 kilodalton assembly. Inactive state holds Arp2 and Arp3 apart preventing nucleation. Upon binding nucleation promoting factor such as WASP WAVE containing VCA acidic domain delivering monomer plus side binding to mother filament via ARPC2 ARPC4 clamp, complex undergoes short pitch activation bringing Arp2 Arp3 together resembling barbed end template. Daughter filament nucleates and elongates with its pointed end capped by Arp2/3 at branch junction, preserving 70 degree angle observed by rotational shadowing. Repeated rounds create dendritic meshwork where growing plus ends push membrane outward, generating force for lamellipodia advancement, phagocytic cup closure and Listeria comet propulsion. Arp2/3 does not depolymerize filaments like cofilin, does not stabilize microtubules which is MAP function, nor transport organelles as myosin does, its core function is branched nucleation.

Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 16: Arp2/3 Complex and Branched Nucleation.

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A Cell Signaling

Overexpression of which GTPase in GTP-bound form modulates actin cytoskeleton?

Rho (GTP), is consistent with established principles of cell signaling, receptor pharmacology and cellular regulation. Experimental measurements of binding parameters, genetic loss-of-function studies and pharmacological interventions all converge on the same interpretation. Related options address neighboring concepts but do not satisfy the precise criterion stated in the question.

Ref: NCERT Biology Class 11–12 Alberts et al Molecular Biology of the Cell Lodish et al, Molecular Cell Biology Cooper & Hausman, The Cell Abbas et al., Cellular and Molecular Immunology (for immunology sections)

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