GN 2.1.2 Flashcards
What is the typical inheritance pattern of non-motile ciliopathies? What two dz’s covered in this lecture that break this pattern?
Autosomal recessive; VHL and PKD can be autosomal dominant
What is the main usage of primary cilia?
Signaling
What are the two types of cilia?
Motile and Non-motile primary cilia
What types of cilia typically occurs as a bundle on one cell?
Motile
What are the two components of the centrosome found at the base of the cilium?
Basal body (mother centriole) and daughter centriole
What is the process that builds and maintains cilia?
Intraflagellar Transport (IFT)
What is the function of motile cilia?
Beating, movement
In what cellular phase does the cilium sprout?
Early G1 or G0
What is responsible for bringing structural and signaling molecules to the cilium from the golgi?
BBSome
What are the five types of signals that primary cilium react to?
Morphogens, Flow/movement, Light, Chemical signals, and Growth factors
Draw a venn diagram that compares developmental disorders and cancer with an overlapping region called neoplasia renal cysts?
Look at venn diagram.
What is the overarching term for motile ciliopathies?
Primary Ciliary Dyskinesia (PCD)
The threshold level of function of which cellular proteins is critical to the progression of ADPKD?
Polycystin-1/2. When PC-1 and PC-2 fall below the function threshold, the dz ensues.
What is the inheritance pattern of PKD (polycystic kidney dz)?
Autosomal recessive or autosomal dominant
What are the two protein modules of the transition zone?
NPHP (nephronophthisis) and MKS (Meckel-Gruber syndrome)
What is the typical arrangement of primary cilia? Where are they typically found?
Singular cilium on apical surface of one cell. Found on almost all vertebrate cells
What clinical manifestation occurs in almost all ciliopathies?
Renal cysts
What is the purpose of the Transition Zone? What would happen if the TS was defective?
The transition zone is the gatekeeper of the cilium. If the TS was defective, there would be abnormal cellular components found in the cilia.
What two ciliopathies predisposes the individual to cancer?
Von Hippel Lindau and Birt Hogg Dube
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)?
Calcium (PIC)
Tolvaptan inhibits the receptor of what molecule therefore inhibiting intracellular cAMP formation?
Vasopressin
What two cellular components are used in anterograde transport?
Kinesin-2 and IFT Complex B
What two cellular components are used in retrograde transport?
Dynein and Complex A
How would you describe the genes affected in both VHL and Birt Hogg Dube?
Tumor Suppressor genes
What cerebral defect is clinically indicative of Joubert’s syndrome?
“molar tooth sign” - a developmental defect of the cerebellum
Draw what a cilia would look like in these 4situations: wt, IFT-B defective, IFT-A defective, defective dynein.
Look at image
What are the ciliary dz’s that present with obesity?
Barder-Biedl Syndrome (BBS) and Alstrom Syndrome
What are the microtubule structural compositions of motile cilia and primary cilia?
Motile: “9+2” (9 doublets with 2 MT in the center) Primary: “9+0”
What is the clinical triad of the autosomal recessive Meckel Gruber syndrome?
Encephalocele, polydactyly, renal cysts
What are five common clinical manifestations of PCD?
Hydrocephalus, Respiratory abnormalities, Laterality defects (situs inverus), Congenital heart defects, Infertility
What are some the components that could be defective in a PCD?
Inner/outer dynein arm, central pair of MT, radial spoke, Nexin-dynein regulatory complex
ADPKD is the fourth leading cause of what condition in the US?
End stage renal dz
What treatment for ADPKD is available in Japan, Europe, and Canda but not the US?
Tolvaptan
What is the role of cAMP in PKD cells?
cAMP is mitogenic for PKD cells. In normal cells it is antimitogenic. PKD cells have high concentrations of PKD within them.
What two components of the motile cilia provide motility?
Dynein arms and central MT pair
What are the symptoms of ADPKD?
HTN, flank pain, hematuria, urinary concentrating defects, nephrolithiasis, urinary tract infections, renal failure, cysts in other organs, hyperlipidemia, aneurysms
What are the non-motile ciliopathies?
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)
Which gene is responsible for 85% ADPKD? Which gene is responsible for 15% ADPKD?
85% - PKD1 15% - PKD2
What is the role of Tolvaptan?
Blocking vasopressin and lowering cAMP levels
What is the most common ciliary chondrodysplasia?
Jeune Syndrome (skeletal dysplasia- narrow ribs, shortened fingers)
