GN 2.1.2

Question 1

What is the typical inheritance pattern of non-motile ciliopathies? What two dz’s covered in this lecture that break this pattern?

Answer 1

Autosomal recessive; VHL and PKD can be autosomal dominant

Question 2

What is the main usage of primary cilia?

Answer 2

Signaling

Question 3

What are the two types of cilia?

Answer 3

Motile and Non-motile primary cilia

Question 4

What types of cilia typically occurs as a bundle on one cell?

Answer 4

Motile

Question 5

What are the two components of the centrosome found at the base of the cilium?

Answer 5

Basal body (mother centriole) and daughter centriole

Question 6

What is the process that builds and maintains cilia?

Answer 6

Intraflagellar Transport (IFT)

Question 7

What is the function of motile cilia?

Answer 7

Beating, movement

Question 8

In what cellular phase does the cilium sprout?

Answer 8

Early G1 or G0

Question 9

What is responsible for bringing structural and signaling molecules to the cilium from the golgi?

Answer 9

BBSome

Question 10

What are the five types of signals that primary cilium react to?

Answer 10

Morphogens, Flow/movement, Light, Chemical signals, and Growth factors

Question 11

Draw a venn diagram that compares developmental disorders and cancer with an overlapping region called neoplasia renal cysts?

Answer 11

Look at venn diagram.

Question 12

What is the overarching term for motile ciliopathies?

Answer 12

Primary Ciliary Dyskinesia (PCD)

Question 13

The threshold level of function of which cellular proteins is critical to the progression of ADPKD?

Answer 13

Polycystin-1/2. When PC-1 and PC-2 fall below the function threshold, the dz ensues.

Question 14

What is the inheritance pattern of PKD (polycystic kidney dz)?

Answer 14

Autosomal recessive or autosomal dominant

Question 15

What are the two protein modules of the transition zone?

Answer 15

NPHP (nephronophthisis) and MKS (Meckel-Gruber syndrome)

Question 16

What is the typical arrangement of primary cilia? Where are they typically found?

Answer 16

Singular cilium on apical surface of one cell. Found on almost all vertebrate cells

Question 17

What clinical manifestation occurs in almost all ciliopathies?

Answer 17

Renal cysts

Question 18

What is the purpose of the Transition Zone? What would happen if the TS was defective?

Answer 18

The transition zone is the gatekeeper of the cilium. If the TS was defective, there would be abnormal cellular components found in the cilia.

Question 19

What two ciliopathies predisposes the individual to cancer?

Answer 19

Von Hippel Lindau and Birt Hogg Dube

Question 20

ADPKD cells produce less of which molecule that results in a lack inhibition of B-Raf (that ultimately allows cAMP to signal for increased cellular proliferation via ERK)?

Answer 20

Calcium (PIC)

Question 21

Tolvaptan inhibits the receptor of what molecule therefore inhibiting intracellular cAMP formation?

Answer 21

Vasopressin

Question 22

What two cellular components are used in anterograde transport?

Answer 22

Kinesin-2 and IFT Complex B

Question 23

What two cellular components are used in retrograde transport?

Answer 23

Dynein and Complex A

Question 24

How would you describe the genes affected in both VHL and Birt Hogg Dube?

Answer 24

Tumor Suppressor genes

Question 25

What cerebral defect is clinically indicative of Joubert’s syndrome?

Answer 25

“molar tooth sign” - a developmental defect of the cerebellum

Question 26

Draw what a cilia would look like in these 4situations: wt, IFT-B defective, IFT-A defective, defective dynein.

Answer 26

Look at image

Question 27

What are the ciliary dz’s that present with obesity?

Answer 27

Barder-Biedl Syndrome (BBS) and Alstrom Syndrome

Question 28

What are the microtubule structural compositions of motile cilia and primary cilia?

Answer 28

Motile: “9+2” (9 doublets with 2 MT in the center) Primary: “9+0”

Question 29

What is the clinical triad of the autosomal recessive Meckel Gruber syndrome?

Answer 29

Encephalocele, polydactyly, renal cysts

Question 30

What are five common clinical manifestations of PCD?

Answer 30

Hydrocephalus, Respiratory abnormalities, Laterality defects (situs inverus), Congenital heart defects, Infertility

Question 31

What are some the components that could be defective in a PCD?

Answer 31

Inner/outer dynein arm, central pair of MT, radial spoke, Nexin-dynein regulatory complex

Question 32

ADPKD is the fourth leading cause of what condition in the US?

Answer 32

End stage renal dz

Question 33

What treatment for ADPKD is available in Japan, Europe, and Canda but not the US?

Answer 33

Tolvaptan

Question 34

What is the role of cAMP in PKD cells?

Answer 34

cAMP is mitogenic for PKD cells. In normal cells it is antimitogenic. PKD cells have high concentrations of PKD within them.

Question 35

What two components of the motile cilia provide motility?

Answer 35

Dynein arms and central MT pair

Question 36

What are the symptoms of ADPKD?

Answer 36

HTN, flank pain, hematuria, urinary concentrating defects, nephrolithiasis, urinary tract infections, renal failure, cysts in other organs, hyperlipidemia, aneurysms

Question 37

What are the non-motile ciliopathies?

Answer 37

Bardet-Biedl Syndrome (BBS) - Transport into cilium

Meckel Syndrome (MKS) - Transition zone

Nephronophthisis (NPHP) - Transition zone

Joubert Syndrome (JBTS)

Jeune Syndrome (JS or JATD)

Ellis-van Creveld Syndrome (EVC) Usher Syndrome (US)

Question 38

Which gene is responsible for 85% ADPKD? Which gene is responsible for 15% ADPKD?

Answer 38

85% - PKD1 15% - PKD2

Question 39

What is the role of Tolvaptan?

Answer 39

Blocking vasopressin and lowering cAMP levels

Question 40

What is the most common ciliary chondrodysplasia?

Answer 40

Jeune Syndrome (skeletal dysplasia- narrow ribs, shortened fingers)