Cilia & Ciliopathies

Question 1

What 5 components are cilia made of?

Answer 1

1. Outer sheath: ciliary membrane
2. Transporters: Intraflagellar Transport
3. Scaffold Structure: axoneme
4. Linkage Domain: Transition Zone
5. Base Anchor: Basal Body

Made of 1000s of proteins

Question 2

What is the basic structure of cilia?

Answer 2

microtubules with + & - ends

• A singlet
• B fused = doublet (CILIA)
• C fused = triplet (BASAL BODIES)

Question 3

What is the function of the basal body?

Answer 3

base anchor that organizes ciliary axoneme

Question 4

What is the function of the axoneme?

Answer 4

structural scaffold of the cilia

Question 5

What is the function of the transition zone?

Answer 5

Ciliary gate keeper

Question 6

What is the function of the ciliary membrane?

Answer 6

continuous with plasma membrane, but different contents

- no ribosomes

Question 7

What is the function of the intraflagellar transport?

Answer 7

organize inside of the cilia
Transport contents
- Kinesin toward + end
- Dynenin toward - end

Question 8

How are cilia formed?

Answer 8

mother centerole (older) becomes basal body
- golgi derived vesicle docks at motehr centrile -> initiate ciliogenesis
-> budding -> actin myosin coupling
-> ciliary sheath completed
=> dock and inserted into plasma membrane

Question 9

How are motile and sensory cilia different?

Answer 9

propel cell + dyenin + 9+2 conformaition
v.
transmit signals from out side world 0 dyenin 9 conformation

Question 10

What are the benefits/ uses of sensory cilia?

Answer 10

concentration of signal
localized
polarized
fluid mechanics
charge disruption
flow sensing

Question 11

What types of things do sensory cilia sense?

Answer 11

physical stimuli
- mechanical strain
- temperature
- osmolality
- gravity
light
chemical stimuli
- hormones 
- chemokines
- growth factors
- morphogens

Question 12

What are some of the responses to the information sensed by the cilia?

Answer 12

cellular proliferation
cellular motility
polarity
growth
differentiation
tissue maintenance

Question 13

What is the significance of the hedgehog protein?

Answer 13

require localized membrane bound organelle to function and sense signaling cues!
OFF
- normal on cilia
ON
- exits cilia -> -> -> activate gli 
=> cell growth & division

Question 14

What are some of the processes that hedgehog signaling contribute to?

Answer 14

limb formation (growth, digit #, polarity)
Bone formation (cell prolif, diff, growth)
Neurogenesis (neural tube form, cralial-facial morph, diff, cell migration)

Question 15

How is the R-L axis determined?

Answer 15

Motile cilia at ciliary node -> rotate 1000x/min -> create flow left to right -> primary sensory sense and respond to flow!

Question 16

What is bardet-biedl syndrome?

Answer 16

Autosomal recessive - 15 known mutations

• involved in formation an maintenance of cilia
• vesicle transport, microtubule anchoring, intraflagellar transport, ubq. med. degredation

Sx:

• photoreceptor degeneration
• anosmia
• mental retardation/ developmental delay
• neural tube defects
• obesity
• hypogonadism
• kidney defects
• polydactly
• diabetes
• situs invertus

Question 17

How are cilia involved in polycystic kidney disease?

Answer 17

genetic (dom and recessive forms)
- related to Ca++basal signalling
- mutations in polycystins (flow and mechanosensor channels) -> incude prolif & cystogenesis 
- important in renal tube cell morphogenesis, maintenance and repair
Sx:
- renal cysts
- liver and pancreas cysts
- intracranial aneurysms