Hitchcock - Cyto 2

Question 1

3 classes of cytoskeletal motors

Answer 1

Kinesin - moves things from the - end to the + end of microtubules. (Pneumonic = Kendrick Perkins = KP = Kinesins go to positive)
Dynein - moves things from the + end to the - end of microtubules
(Pneumonic = Dirk Nowitzki = DN = Dyneins go to negative)
Myosin - Moves things from the - end to the + end of actin filaments

• All convert the energy of hydrolysis of ATP (to ADP and Pi) into mechanical work. The binding of ATP causes a conformational change in the motor. The rate limiting step in this process is the release of product (Pi) following hydrolysis, but this is sped up by binding to actin or microtubule (they act somewhat like a GEF). One possible area of regulation can be in the area of accelerating Pi release, which will accelerate strong binding between the actin and myosin.
• Vesicles can have multiple types of motors on it so that it can travel on microtubules and actin filaments.

Question 2

Primary Ciliary Dyskinesia (PCD) = Kartegenner SYndrome

Answer 2

Dynein is made but doesn’t become part of the cilia. Mutation in outer arm of dynein. The cilia are therefore immotile, causing respiratory tract infections as well as sterility in males (sperm don’t move). Also associated with Situs Inversus

Question 3

Cell migration

Answer 3

The lamellopodium is the leading edge, which is protruding. The back end is contracting.

Question 4

Dynactin

Answer 4

multifunctional protein complex that helps dynein to bind to microtubules and other proteins. It binds to the tail region of dynein.

Question 5

Myosin V

Answer 5

Basically, Melanin is contained in vesicles called melanosomes. They are transported on microtubules and actin filaments to the periphery of the cell where they are taken up by keratinocytes. Myosin V is required for transport to the periphery.

• Myosin V binds its cargo via melanophilin (Mlph), which is bound to Rab27aGTP, which is bound to the melanosome.
• If Myosin V, Rab27aGTP, or melanophilin is mutated, there will be no melanosomes at the periphery of the cell - they will remain in the basal level of the epithelium - and the animal will be pale. In humans this causes Griscelli Type 1 and Elejalde syndromes. These cause silvery hair, sever neurological defects, and light skin in a child with dark-skinned parents.

Question 6

mechanism of Myosin and Kinesin

Answer 6

It is the binding of ATP that causes the release of myosin from actin. Once it is released, it is the weak binding of the ADP bound Myosin that will cause the Pi release and then strong binding. Once this happens there will be a power stroke.
- head binds beta tubulin. Leading head has no ATP, trailing head has ADP. When ATP binds the leading head, the trailing head steps over along the filament. The trailing head then hydrolyzes it’s ADP and comes off of the filament.

Question 7

Griscelli

Answer 7

when there is a mutation in anything in the melanosome pathway, so rab27GTP, malenophilin, the myosin V. Kid will have gray hair