13 public questions tagged with this topic.
Microtubules form tracks along which organelles and vesicles move within the ll, facilitating intracellular transport. This follows from NCERT principle where the relation explains the outcome clearly for students in simple steps.
Ref: NCERT Biology Textbook for Class XI and XII (Botany section), Chapter: Cell Structure and Function, Cell Cycle and Biomolecules, Topic: Cell organelles and biomolecular structure.
Cytoskeleton provides scaffold and track system built from protein polymers regulated by nucleation factors, GTPases, and post-translational modifications. Actin filaments, 7 nanometer diameter polarized structures polymerizing from ATP-G-actin mediated by Arp2/3 complex branching at 70 degrees and formins nucleating straight cables for filopodia, associate with myosin II for contractility at cortex and myosin V for short-range vesicle transport near cell periphery, driving lamellipodia extension and endocytic invagination. Microtubules, 25 nanometer hollow tubes of alpha-beta tubulin dimers w
Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 16: Cytoskeleton and Intracellular Transport.
Endocytic trafficking relies on progressive maturation and sorting of internalized cargo to maintain membrane homeostasis and signaling fidelity. Early endosomes, also called sorting endosomes, receive clathrin-coated and non-clathrin vesicles from the plasma membrane containing receptors such as transferrin receptor, EGF receptor, ligands, low-density lipoprotein, and extracellular fluid. Their pleomorphic tubular-vesicular morphology and mildly acidic pH around 6.0 to 6.2, maintained by vacuolar ATPase delivering protons, facilitate dissociation of many ligands from receptors while preservin
Ref: Alberts et al., Molecular Biology of the Cell, 6th ed., Chapter 13: Intracellular Vesicular Traffic – Early Endosomes and Sorting.
Although dynein can bind microtubules and hydrolyze ATP alone in vitro motility assays in vivo most physiological functions require dynactin 1 MDa multiprotein complex discovered as activator of vesicle transport from squid axoplasm. Structure comprises Arp1 actin related protein filament 8 copies forming short filament 37 nm rod barbed end capped by CapZ pointed end by Arp11 p62 p25 p27 complex shoulder arm containing p150Glued DCTN1 with N terminal CAP Gly plus basic microtubule binding domains and long coiled coil dimer interacting with dynein intermediate chain via CC1 box. Dynactin perfor
Ref: Schroer, Annu Rev Cell Dev Biol 2004 – Dynactin function linking dynein to cargo and enhancing processivity.
Kinesin-1 regulation avoids gratuitous ATP consumption and traffic jams by autoinhibition mechanism evolutionarily conserved ensuring motor only active when bound to cargo. In cargo free state heavy chain tail IAK motif folds back contacting motor head switch regions blocking microtubule stimulated ADP release maintaining ATPase low about 10 fold inhibition. Light chains also contribute to folded globular conformation compact. Cargo adaptors such as JNK interacting proteins JIP1-3 FEZ1 Milton TRAK bind light chains or tail sterically unfolding molecule to extended active state increasing micro
Ref: Verhey & Hammond, Nat Rev Mol Cell Biol 2009 – Kinesin-1 activation by cargo binding unfolding mechanism.
Myosin V stride size uniquely adapted to actin filament helical symmetry enabling straight long distance walks without spiraling around filament axis. The molecule possesses six IQ motifs per heavy chain creating extended lever about 24 nm much longer than myosin II lever. During processive movement heads alternate hand over hand trailing head detaches after ATP binding swings forward as lever rotates about 100 degrees. Actin filament repeats every 13 monomers corresponding to 36 nm axial distance where binding site orientation repeats facing same direction. Center of mass therefore advances 3
Ref: Mehta et al., Nature 1999; Purcell et al., PNAS 2005 – Myosin V 36 nm center and 72 nm head step mechanism.
Myosin V is prototypical class V unconventional myosin that operates on actin filaments not microtubules serving local delivery after long range microtubule transport. The molecule is dimeric with two motor heads each containing six calmodulin or essential light chain IQ motifs forming a 24 nm lever arm, a coiled coil stalk and a globular tail domain that binds cargo adaptors such as Rab11, Rab27, melanophilin and Myo4p binding proteins. It moves processively hand over hand toward barbed plus end near plasma membrane hydrolyzing one ATP per step with coordinated gating that prevents simultaneo
Ref: Vale, Cell 2003; Hammer & Sellers, Nat Rev Mol Cell Biol 2012 – Myosin V processive transport on actin filaments.
Intracellular cargo trafficking covers both microtubule and actin routes. Long range 10 to 100 micron interphase transport uses kinesin dynein on microtubules, while short range local transport within cortical actin rich zones 1 to 10 micron uses myosin. Processive myosin capable of multiple steps without dissociation required for efficient transport. Myosin V class features high duty ratio spending about 70 percent cycle strongly attached, dimeric coiled coil tail, six IQ motifs with calmodulin light chains per head forming long 24 nanometer lever arm achieving 36 nanometer step matching heli
Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 17: Myosin V and Cargo Transport.
Two distinct superfamilies of cytoskeletal motors evolved to walk along filaments using ATP hydrolysis. Myosin motors share N terminal head motor domain containing actin binding interface including helix turn helix, cardiomyopathy loop, P loop ATPase, Switch I II for gamma phosphate sensing and lever arm with IQ motifs binding calmodulin light chains. Upon interaction with F actin 7 nanometer helical filament, head undergoes conformational cycle releasing phosphate driving swing of lever arm producing force along filament. Diverse isoforms specialize: myosin II non processive forming bipolar f
Ref: Alberts et al., Molecular Biology of the Cell, 7th ed., Chapter 16: Myosin Motors and Actin Filaments.
Coat assembly regulated spatiotemporally to occur only at correct donor membranes and when cargo present ensuring energy not wasted. Initiating event activation of small GTPases Sar1 and ARF families from GDP cytosolic to GTP membrane state. Sar1 activated by Sec12 GEF integral ER protein exchanges GDP for GTP exposing amphipathic helix embedding ER leaflet inducing curvature recruiting Sec23-Sec24 heterodimer. Similarly ARF1 activated by GBF1 at ERGIC cis-Golgi and BIG1/2 at TGN upon membrane recruitment exposes myristoylated helix plus effector binding switch regions recruiting COPI coatomer
Ref: Lee & Miller, Annu Rev Cell Dev Biol: Sar1 and ARF GTPases initiate coat assembly.
Assembly of heteromeric SNARE core provides mechanical work for fusion in neurons, endocrine cells and constitutive secretion. Proteins classified into Q-SNAREs supplying glutamine at central zero ionic layer and R-SNAREs supplying arginine. Target plasma membrane harbors two Q proteins: syntaxin1 integral with single Q helix preceded by Habc regulatory domain clamped by Munc18 and SNAP-25 peripheral anchored via palmitoylated linker contributing two Q helices lacking transmembrane domain together contributing three Q motifs collectively t-SNARE. Vesicle membrane supplies R protein synaptobrev
Ref: Jahn & Scheller, Nat Rev Mol Cell Biol: SNAP-25 as Qbc t-SNARE in fusion.
Vesicle fusion fidelity beyond tethering relies on SNARE proteins providing thermodynamic driver for bilayer merger overcoming hydration repulsion. Vesicle membranes contain R-SNAREs like synaptobrevin VAMP2 with single motif and C-terminal anchor, while target membranes harbor Q-SNAREs syntaxin family with Habc regulatory domain and SNAP-25 family contributing two motifs anchored by palmitoylation. When opposed membranes brought within few nanometers by Rab tethers and multisubunit complexes, oppositely oriented SNARE motifs assemble as parallel four-helix coiled coil from N-terminus to C-ter
Ref: Jahn & Scheller, Nat Rev Mol Cell Biol 2006: SNARE four-helix bundle drives membrane fusion.
