Cytoskeleton Flashcards
What holds filaments together?
Weak non-covalent interactions
What shape do filaments usually have?
Helices joined together laterally.
What are 3 major roles of microtubules?
- Organelle transport (tracks)
- Cilia and flagella
- Cell division
Describe the microtubule structure.
2 tubulin subunits: alpha and beta forma hetrodime
How do microtubules grow?
MTOC nucleate the growth at the minus end with the plus end growing away from it. Facilitated by MAPS (e.g. Tau).
What drugs affect microtubule function?
KN_ [Taxol (binds and occupies)
Colchicine (prevents polymerization)
Vinblastine (prevents polymerization)
What roles do actin play?
- Cell shape
- Cell locomotion
- Cytokinesis
- Phagocytosis
- Platelet aggregation
What are the 6 classes of intermediate filaments?
- Lamins
- Keratins
- Neurofilaments
- Vimentins
- GFAP (glia)
- Desmin
What are the 3 steps of cell movement?
- Protrusion of the leading edge
- Adhesion of the leading edge/deadhesion of trailing edge
- Movement of the cell body
What structure operates at the protruding edge of actin cytoskeletons?
Lamellipodia, thin sheet-like projections that pull cells through tissues.
What is behind the lamellipodia?
A more stable region of lamella which couples the actin network to myosin II-mediated contractility substrates (e.g. ECM of another cell)
What severs the ends of existing actin filaments in response to growth factors or other signals?
Cofilin
Describe the activation of actin nucleation.
Rac1, a Rho GTPase, is activated/PIP2 -> activates WAVE complex (a type of WASP -> Wave complex uses molecules Arp2/3 to generate a branched actin network.
What protects the + end of actin filaments?
Formin family proteins
What are integrins composed of?
Heterodimers: alpha and ebta subunits
What are the adhesion sites composed of?
Fibronectin in the ECM binds the extracellular portions of integrins. These points serve as traction points for contractile forces.
What do adhesion points do (other than adhere)?
Regulate Rho GTPases to control polymerization and organization of actin!
How does the trailing edge detach?
- Rho A, a Rho GTPase, inhibits Rac1 to prevent lamellipodia formation and actomyosin contractility.
- Microtubule-induced adhesion disassembly.
- Integrin endocytosis
- proteolytic cleavage of linker proteins.
How does the cell body move?
Molecular clutching, a process that integrates adhesion, retrograde flow, and actin polymerization.
What is non-muscle myosin II (NMII)?
A motor protein/ATPase that moves along actin filaments towards the PLUS end (actin filaments provide the track, myosin motor, and AT the energy). This is retrograde flow(??)
Describe the structure of NMII.
Globular head (binds actin and ATP)
Light chain linkers (ELC + RLC)
Helical heavy chain
What happens when the molecular clutch is disengaged?
Actin is not anchored to the substratum and actin polymerization is counterbalanced by retrograde flow: no movement!
What happens when the molecular clutch is engaged?
Actin is coupled to ECM and retrograde flow is impeded b the ECM. New actin polymerization exceeds retrograde flow and the cell moves forward.
The ____ chain of the microtubule is the fastest growing.
Beta
Can both ends of a microtubule both grow and depolymerize?
Yes
In microtubules, the ____ end grows fastest.
+
What is the function of gamma tubulin?
Functions as a template for the correct assembly of microtubules
What stabilizes the end of of microtubules?
Capping proteins
What are MAPS
Microtubuels-associated proteins can stabilize/destabilize/regulate, etc.
What does taxol do?
Stabilize microtubules. Used to treat breast cancer, lung cancer, ovarian cancer, Kaposi’s sarcoma.
What drugs prevent microtubule polymerization?
Colchicine and Vinblastine
What does Colchicine treat?
Gout
Familial Mediterranean Fever
What does Vinblastine treat?
Testicular and breast caners
Lymphomas
Kaposi’s sarcoma
What is the final intermediate filament assembly?
Eight tetramers twisted into a rope-like structure.
What are the 3 types of actin monomer subunits?
Alpha
Beta
Gamma
One actin subunit is made of ____ type of actin.
One
One strand of actin is amde of ____ actin subunits.
2
What types of messengers cause actin filaments to reorganize and move?
Growth factors (e.g. PDGF, EGF, VEGF)
Amino acids
Second messengers (e.g. Ca2+)
Formylated peptides
Detachment of the lagging edge is regulated by ____.
Rho A (also a GTPase)
Each step of NMII corresponds with hydrolysis of how many ATP?
One
What are the 4 steps of movement in actin-myosin contraction?
- Actin cytoskeleton coupled to the ECM by interaction of actin-binding proteins with integrins.
- Actin polymerization at front of cell pushes out membrane: leading edge
- Actomyosin contraction pulls the rear of the cell forward.
- The cell moves
