Cilia and ciliopathies Yo Flashcards Preview

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Flashcards in Cilia and ciliopathies Yo Deck (19)
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1
Q

5 Components of cilia

A
  1. Basal body: base anchor
  2. Axoneme: scaffold structure
  3. Transition zone: linkage domain
  4. Intraflagellar transport: transporters
  5. Ciliary membrane: outer sheath
2
Q

Basal body
function?
Structure?

A

base anchor from which cilia are formed

-microtubule rich cylinder structure formed from 9 triplet microtubules

3
Q

Axoneme
function?
Structure?

A

structural skeleton of cilium that serve as scaffold and provide tracks for movement w/in cilia

-Formed from doublet microtubule (A-B tubules) of basal body

4
Q

Transition zone

A
  • Links basal body to axoneme.
  • Considered as “gatekeeper”: limits diffusion of membrane and soluble proteins into/out of cilium.
  • Ensures ciliary membrane is a distinct compartment for cellular signaling.
5
Q

Intraflagellar transport

A

Transports signaling components within the cilia via axoneme bidirectionally

  • Kinesin and IFT-B direct movement towards ciliary tip (anterograde transport)
  • Dynein and IFT-A directs movement towards cytoplasm (retrograde)
6
Q

Ciliary membrane

A

continuous with plasma membrane but is compartamentalized by transition zone
–> compositionally distinct membrane with unique phospholipids n receptor molecules

7
Q

How are cilia assembled (ciliogenesis)

A

By centriole formation and cilium formation:

  1. Centriole dup. occurs during G1 to S-phase
    • one older “maternal centriole” and 1 young
  2. Centrioles assemble/pair
  3. Distal end of basal body is capped
    by “ciliary vesicle”
  4. Microtubule doublets assemble into ciliary vesicle
  5. Entire structure fuses with PM
8
Q

Motile Cilia

A

required for movement of fluid in respiratory, neural, and reproductive tracts

-produced by axonemal dynein dependent sliding motion btwn double microtubules

-have 9+2 arrangement
(9 double microtubules organized around central pair of singlet microtubule)

(most motile cilia also have sensory functions)

9
Q

Sensory Cilia

A

aka Non-motile aka primary cilia
have signalling function

  • lack axonemal dynein arms
  • have a 9+0 microtubule arrangement
10
Q

Why are cilia used for signaling?

A

Cilia are the cell’s antennae
allows for:

  1. Concentration of signal
  2. localization of signal
  3. polarizing signal
  4. fluid mechanics
  5. charge disruption
  6. flow sensing by mechanical bending

These produce downstream events

11
Q

Downstream events of cilia signaling

A
  1. Cellular proliferation
  2. cellular motility
  3. polarity
  4. growth
  5. differentiation
  6. tissue maintenence
12
Q

Signaling pathways that function through cilia

A
  1. Hedgehog (Hh) signaling pathway
  2. Activation/Repression of Hh paracrine signaling pathway (Gli transcriptional activator)
  3. Wnt, PDGF, FGF
13
Q

Examples of how cilia function in development and homeostasis

A

Motile and immotile cilia are important.

  • limb formation
  • bone formation and homeostasis
  • neurogenesis
  • polarity
  • neural tube formation

AND MUCH MUCH MORE IM NOT WRITING

14
Q

Characteristics of cilial syndromes

A
  1. cystic kidneys
  2. nephronophthisis

Many more that can affect along process of cilia formation.

15
Q

Clinical features / defects associated with ciliopathies

A
  1. Rare.
  2. Pleiotropic.
    - Each ciliopathy is characterized by different clinical outcomes.
  3. Overlapping.
    - Most of the ciliopathies have overlapping phenotypes and genetic
    mutations.
  4. Structural.
    - Mutations often affect core cilium structure and function.
  5. Diverse.
    - ~50 genes are known to be mutated in ciliopathies to date.
  6. Genetically complex.
    - Mutations in the same gene (Cep290) can produce four
    different clinical outcomes
16
Q

Bardet-Biedl Syndome (BBS):

  • mode of inheritance?
  • what proteins are affected?
A

autosomal recessive

- BBS proteins typically participate in protein complex required for vesicle transport within the cilium

17
Q

Bardet-Biedl Syndome (BBS) symptoms

A
  • Photoreceptor degeneration
  • Anosmia
  • Mental retardation / Developmental delay
  • Neural tube defects
  • Obesity
  • Hypogonadism
  • Kidney defects
  • Polydactyly
  • Diabetes
  • situs inversus
18
Q

Polycystic Kidney Disease (PKD):

  • mode of inheritance?
  • what genes are affected?
A

Autosomal dominant

  • ADPKD
  • caused by mutation in polycystin-1 and 2 (PKD1 and PKD2)

Autosomal recessive

  • ARPKD
  • caused by fibrocystin mutations
19
Q

Polycystic Kidney Disease (PKD): symptoms

A

Symptoms:
• Renal cysts
• Liver and pancreas cysts
• Intracranial aneurysms