Cytoskeleton and Extracellular Matrix

Vocabulary flashcards covering cytoskeleton components, cytoskeletal regulators, cell‑cell and cell‑ECM attachments, and extracellular matrix components mentioned in the lecture.

Actin filaments (F‑actin)

Filaments formed by polymerization of G‑actin monomers; provide structural support and mobility; polarized with a barbed (plus) end and a pointed (minus) end.

G‑actin vs F‑actin

G‑actin is the globular monomer; F‑actin is the polymerized filament; polymerization occurs primarily at the barbed end.

Barbed end vs pointed end

Barbed (plus) end favors rapid addition of actin subunits; pointed (minus) end grows more slowly.

Nucleation

Initial formation of actin oligomers that seeds filament formation; rate‑limiting step in polymerization.

ATP role in actin polymerization

ATP binding to G‑actin promotes polymerization; after incorporation, actin hydrolyzes ATP to ADP, reducing affinity and promoting turnover.

ATP hydrolysis in actin filaments

Hydrolysis of ATP after incorporation weakens subunit interactions, contributing to filament dynamics.

Actin‑ADP binding affinity

Actin bound to ADP has lower affinity for the filament, promoting turnover and disassembly.

Formin

Actin nucleation factor that binds actin‑ATP and promotes nucleation, adding actin to the barbed end of unbranched filaments.

Profilin

Protein that exchanges ADP for ATP on G‑actin, supplying ATP‑bound actin for polymerization.

Arp2/3 complex

Nucleates branched actin filaments, creating dendritic networks; activated by WAS family proteins.

Capping proteins

Bind to filament ends to prevent addition or removal of subunits, regulating filament growth.

Cofilin

Binds and severes actin filaments, generating new ends for polymerization and increasing turnover.

Tropomyosin and troponins

Regulate access of myosin to actin filaments; crucial for muscle contraction control.

Wiskott‑Aldrich Syndrome (WAS)

X‑linked loss‑of‑function WAS gene; WASP activates Arp2/3 to promote branched actin growth; causes microthrombocytopenia and immune defects.

Dystrophin‑glycoprotein complex

Links actin cytoskeleton to the extracellular matrix via dystroglycans and associated proteins; stabilizes muscle cell membranes.

Duchenne muscular dystrophy (DMD)

X‑linked dystrophin deficiency; elevated blood CK; cardiomyopathy; delayed motor development and Gower maneuver.

Becker muscular dystrophy (BMD)

Dystrophin truncation with reduced function; typically milder than DMD.

Microtubules

Hollow polymers of α‑ and β‑tubulin dimers; typically 13 protofilaments; polar with plus and minus ends; serve in shape, transport, and mitosis.

α‑ and β‑tubulin dimers

Subunits that assemble into microtubules; GTP binding and hydrolysis regulate dynamics.

Protofilaments

Linear chains of tubulin dimers that assemble into the hollow microtubule tube (typically 13).

GTP cap concept

GTP‑bound tubulin at the plus end stabilizes growth; hydrolysis to GDP promotes catastrophe and shrinkage.

MAPs (microtubule‑associated proteins)

Proteins that regulate microtubule dynamics; can act as polymerases to promote growth.

Depolymerases and catastrophe

Proteins that promote disassembly of microtubules; loss of the GTP cap leads to rapid shrinkage.

Centrosome and γ‑tubulin ring complex (γ‑TuRC)

Microtubule organizing center; γ‑TuRC nucleates microtubules from the centrosome.

Kinesins

Plus‑end–directed motors that move cargo away from the nucleus along microtubules.

Dyneins

Minus‑end–directed motors that move cargo toward the nucleus along microtubules.

Cilia and flagella (9+2)

Motile appendages with an axoneme: nine doublet microtubules surrounding two central microtubules; power by dynein.

Movement of cilia/flagella

Dynein motor activity slides microtubules; nexins and bending generate propulsion.

Microvilli and actin bundles

Protrusions with tightly packed parallel actin bundles; fimbrin and villin organize bundles.

Pseudopodia, lamellipodia, filopodia

Actin‑based cell surface projections involved in movement and exploration of the environment.

Myosin II and contractile ring

Myosin II generates contractile force in the cytokinetic ring during cell division by sliding actin filaments.

Unconventional myosins (I and V)

Myosin I associates with membranes; myosin V transports vesicles along actin filaments.

Intermediate filaments (IFs)

Apolar, rope‑like cytoskeletal filaments formed by coiled‑coil dimers that assemble into tetramers and protofilaments.

IF assembly and structure

Dimer → antiparallel tetramer → protofilament → ~8 protofilaments forming a rope‑like filament.

IF protein types (examples)

Keratins (acidic/basic), vimentin, desmin, GFAP, peripherin, neurofilament proteins, lamins.

Desmosomes and plakins

Desmosomes connect keratin IFs between cells; plakins link IFs to desmosomes and other cytoskeletal elements.

Hemidesmosomes

Attach epithelial cells to the basement membrane via integrins (α6β4) and plectin; connect to IFs.

Cadherins

Calcium‑dependent cell–cell adhesion molecules; mediate homophilic binding between neighboring cells.

Adherens junctions

Cell–cell junctions where cadherins connect to actin cytoskeleton via catenins (β‑catenin, p120).

Desmosomes (junctions)

Cell–cell junctions linking intermediate filaments between adjacent cells via desmosomal cadherins.

Tight junctions

Seal epithelial sheets to prevent paracellular passage and separate apical from basolateral domains.

Gap junctions

Channel‑forming junctions that permit passage of small molecules and ions between cells; formed by connexins.

Connexin 26 (GJB2)

Connexin family member linked to nonsyndromic deafness; key component of gap junctions in the ear.

Epidermolysis bullosa simplex (EBS)

Autosomal dominant/recessive keratin gene mutations causing skin blistering.

Collagen structure

Triple helical collagen with three α chains; every third amino acid is glycine; repeats of hydroxyproline/hydroxylysine.

Collagen folding and glycine spacing

Glycine at every third position allows tight triple‑helix packing; post‑translational modifications stabilize it.

Collagen types I, II, III (fibril‑formers)

Form fibrils in skin, bone, cartilage; provide tensile strength.

Collagen type IV (network)

Network‑forming collagen in basal lamina, forming a sheet‑like network.

Collagen type VII (anchoring)

Anchors basal lamina to underlying connective tissue.

Prolyl hydroxylase and scurvy

Hydroxylation of proline requires vitamin C; deficiency leads to weakened connective tissue (scurvy).

Osteogenesis imperfecta

Mutations in COL1A1 or COL1A2 encoding type I collagen; brittle bones with multiple fractures.

Marfan syndrome

FBN1 mutation; defective fibrillin‑1 microfibrils leading to abnormal TGF‑β signaling; tall stature, aortic aneurysm.

Loeys–Dietz syndrome

Mutations in TGFBR1/2 or SMAD3; features similar to Marfan with earlier and sometimes more severe vascular disease; no ectopic lens.

Elastin fibers

Elastic ECM components providing resilience and elasticity to tissues such as skin and vessels.

Proteoglycans and GAGs

Core proteins bound to sulfated glycosaminoglycans (GAGs); form hydrated gels in ECM; hyaluronan is a non‑sulfated GAG.

Aggrecan

Cartilage proteoglycan with many chondroitin sulfate chains; aggregates with hyaluronan in ECM.

Fibronectin

Major adhesion protein that binds collagen and proteoglycans; recognized by integrins to connect ECM to cells.

Laminin

Major basal lamina glycoprotein; forms networks and binds nidogen to collagen in the ECM.

Fibrillin‑1 microfibrils

Microfibrils composed of fibrillin‑1; sequester TGF‑β in the ECM; mutated in Marfan syndrome.

Basal lamina

Specialized extracellular matrix layer underlying epithelia; supports and separates tissues; rich in laminins and collagen IV.

Focal adhesions

ECM–to–cytoskeleton linkages formed by integrins; involve talin, vinculin, and α‑actinin.

Extracellular Matrix (ECM) overview

Complex network of collagen, elastin, proteoglycans, GAGs, and glycoproteins that provides structure and signaling to tissues.

Glycoproteins and adhesion proteins

Fibronectin and laminin are key ECM glycoproteins that mediate adhesion to integrins and other ECM components.

Ig superfamily CAMs

Cell adhesion molecules (ICAMs, NCAMs) that mediate cell–cell interactions; can be heterophilic or homophilic.

Selectins

CAMs that recognize carbohydrate ligands; L‑selectin, E‑selectin, and P‑selectin mediate leukocyte trafficking and adhesion.

Integrins

Transmembrane heterodimers (α and β) that connect ECM to the cytoskeleton; signal bidirectionally via adaptors like talin and vinculin.

Cadherins (cell‑cell adhesion)

Calcium‑dependent adhesion molecules that maintain tissue architecture by mediating cell–cell contact.

Ig superfamily CAMs vs integrins vs cadherins

Different CAM families with distinct ligands and junctional roles; integrins link ECM to cytoskeleton, cadherins mediate cell–cell adhesion, Ig CAMs mediate varied cell–cell interactions.

Tight junctions vs gap junctions

Tight junctions seal paracellular space; gap junctions permit direct cytoplasmic exchange between adjacent cells.

Autosomal dominant vs recessive keratin mutations in EBS

Autosomal dominant or recessive patterns depending on mutation; disrupts keratin IFs, weakening cell integrity.