Question 3.

Primary ciliary dyskinesia (PCD), also called immotile ciliary syndrome or Kartagener

syndrome, is a rare, ciliopathic, autosomal recessive genetic disorder that causes defects in the action

of cilia lining the respiratory tract (lower and upper, sinuses, Eustachian tube, middle ear), fallopian

tube, and flagella of sperm cells. In PCD the cilia do still have some very low level movement, but in

addition to slower cilia movements these movements are unsynchronized. Respiratory epithelial

motile cilia, which resemble microscopic "hairs" (although structurally and biologically unrelated to

hair), are complex organelles that beat synchronously in the respiratory tract, moving mucus toward

the throat. Normally, cilia beat 7 to 22 times per second, and any impairment in this movement or the

synchrony of movement between cells can result in poor mucociliary clearance, with subsequent

upper and lower respiratory infection.

A. Fully describe all the structural parts of a cilium. (see chapter 16)B.

C.

How does a cilia work? What are all the “parts” needed to make cilia move properly? How do

these “parts” interact to create a moving cilium (also What cell/molecular factors are needed

for cilia on one cell to move in synchrony with the cilia on an adjacent cell or on the same

cell) (see chapter 16)

Explain how cilia are formed at the cellular level, in the respiratory tract of a human. In your

explanation try to be as thorough as possible

—In other words — describe the entire process of cilia biogenesis –from what genes are need

to be initially expressed; what proteins are made from the mRNAs from those expressed

genes; where are these proteins made; that are needed to make the cilia (in the cytosol-on free

ribosomes? or on ER ribosomes). This includes not only the proteins that are physically a part

of the cilia, but also any motor proteins that are cargo transporters and construction proteins

(the machines that build the cilia) For Example how are the proteins that are in the cilia itself

transported from the ribosomes where they are 1st made to the actual plasma membrane site

where the cilia will be newly formed. Are motor proteins needed for this transport event; are

any accessory proteins needed to make this transport possible. Also after all the proteins have

been made—How does the cilia get built. What puts all the pieces of the cilia together—how

does it get elongated what proteins are needed to build it; to lengthen it; to stabilize it ; to

attach its parts to one another. How do these protein factors and other molecular factors

combine…. to go from an initial state of “no cilia present” to the creation of a brand new

cilia.

D.
1)

2)

Based on your description above, of the factors needed for cilia biogenesis (in part C) and

cilia functionality in part B:

Describe a hypothetical genetic mutation that might cause Primary ciliary dyskinesia.

(Give the name of the gene that is being mutated) For this question—Your mutation

should specifically effect the shape of a protein that is needed for cilia biogenesis that

when altered could then directly or indirectly impair the proper formation of cilia or

impair the cilia motility process itself ; as seen in clinical cases of Primary ciliary

dyskinesia. Be sure to explain how and why the mutant protein’s altered structure is

leading to the malfunction in cilia movement.

Describe a hypothetical genetic mutation that might cause Primary ciliary dyskinesia.

(Give the specific name of the gene that is being mutated) For this question—Your

mutation should specifically effect the shape of a protein that is involved in

synchronizing the movement between cilia on adjacent cells……as seen in some clinical

cases of Primary ciliary dyskinesia. Be sure to explain how and why the mutant

protein’s altered structure is leading to the malfunction in cilia synchronization.