Contractile proteins Flashcards
What is the cytoskeleton?
System of filaments scaffolding the cell that helps with structural, spatial and mechanical functions
What is a major component of the cytoskeleton?
Actin
What determines the shape of the cell and its ability to divide?
Actin and actin binding proteins
What uses ATP hydrolysis to move filaments and move organelles along filaments?
Myosin (motor protein)
Each subunit of actin is bound to what and called?
G-actin (globular actin) is bound to an ATP
G-actin subunits assemble into what and are bound to what?
F-actin (filamentous actin) is bound to ADP after it hydrolyzed it to help form a filament
Which end of the F-actin grows faster?
Plus end grows faster and minus end grows slower
Why is polarity of the F-actin important?
It is important for assembly and for establishing a direction of movement of myosin relative to actin
What are the phases of F-actin polymerization?
Nucleation (lag phase) Elongation (growth phase) Steady state (equilibrium phase)
Describe the polymerization of F-actin
G-actin subunits form an oligomer of 3 subunits and then logarithmically grow fast into F-actin
What is the critical concentration of actin?
When the rate of polymerization is equal to the rate of dissociation of actin (steady state)
Where is actin the most abundant?
Right beneath the plasma membrane to provide mechanical support, cell shape and enables cells to migrate, engulf, divide
Actin binding proteins
Organize f-actin into bundles/networks that can then perform the functions of actin - have to have 2 actin binding domains
What are the 2 types of actin bundles?
Parallel bundle and contractile bundle
What protein is used in the parallel bundle?
Fimbrin
Describe parallel bundles?
Actin filaments + fimbrin; Tightly packed to prevent myosin 2 from entering; seen in microvilli to increase surface area, nutrient uptake and signaling of the cell
What protein is used in the contractile bundle?
Alpha-actinin
Describe contractile bundles?
Actin filaments + alpha-actinin; loosely packed to allow myosin 2 to enter; seen in the contractile ring used in mitosis to divide the cell
Compare the size of alpha-actinin
Larger protein in order to increase the distance between actin filaments
What are actin networks?
Actin filaments held together by large actin binding proteins such as filamin that creates a 3D meshwork in order to withstand force and determine stability of membrane
What is spectrin?
Actin binding protein in RBCs that also binds ankyrin and protein 4.1 to control cell deformability/flexibility
Hereditary spherocytosis
Mutations in spectrin, ankyrin, protein 4.1 that results in impaired deformability/flexibility leading to unstable RBCs = spherical RBCs
What are the symptoms of HS?
Jaundice, splenomegaly, anemia and spherical RBCs
What are myosin proteins?
Motor proteins that move along actin filaments via ATP hydrolysis
What are the 3 domains of a myosin protein?
Head, neck, tail
Purpose of the myosin head?
Contains actin binding sites and ATP binding sites as well as ATPase activity
Purpose of myosin neck?
Flexible region that binds myosin light chain peptides
Purpose of myosin tail?
Intertwine, bind membrane and organelles
What are the 3 types of myosin?
Myosin 1, 2, 5
Describe myosin 1
One head
Function = membrane association and endocytosis
Describe myosin 2
2 heavy chains each with head and neck domain; tail homodimerizes
Function = contraction
Describe myosin 5
2 heavy chains and 6 light chains per neck, end of tails associate with specific receptors on organelles
Function = organelle transport
What direction do myosin proteins move?
Towards the plus end of actin
How is the powerstroke related to the myosin neck?
The longer the myosin neck, the greater the rate of movement
What are the important proteins within the sarcomere?
Cap Z, Tropomodulin, nebulin, Titin
Cap Z function
Stabilizes plus end of sarcomere
Tropomodulin function
Stabilizes minus end of sarcomere
Nebulin function
Extends along the length of the actin filament; length determines the length of the actin filament
Titin function
Stabilizes myosin and prevents overstretching
What can titin mutations cause?
Cardiomyopathies - harder for heart to pump blood
How do non-muscle cells contract?
Actin-myosin structures are formed in a transient manner as needed by the cell
Describe the dystrophin protein?
Links the cytoskeleton (actin) of muscle fibers to the cell membrane/connective tissue
Acts as a shock absorber during contraction and stabilizes the sarcolemma to prevent injury to the muscle fibers
What are the 2 types of duchenne’s muscular dystrophy?
Duchennes and beckers muscular dystrophy
How is duchenne’s muscular dystrophy inherited?
X-linked recessive that causes muscle wasting
What kind of mutations does duchenne’s muscular dystrophy have?
Out of frame mutants that create little to no dystrophin
What kind of mutations does becker’s muscular dystrophy have?
In frame mutants that create a smaller protein with partial function
What is the current treatment for duchenne’s muscular dystrophy?
Gene therapy, dystrophin replacement, drugs to prevent exon skipping
