Cilia

Question 1

1. Identify the components of cilia.
2. Explain how cilia are assembled.
3. Explain the differences between motile and sensory cilia.
4. Identify signaling pathways that function through cilia and explain why cilia are used for signaling.
5. Provide examples of how cilia function in development and tissue homeostasis.
6. Recognize the clinical features and cilia defects associated with ciliopathies.

Answer 1

x

Question 2

The basal body is composed of _____, the axoneme composed of_____.

Answer 2

triplet radial microtubule repeats; double radial microtubule repeats

Question 3

Motile cilia have _____ and are arranged in a _____.

Answer 3

dynein arms; 9x2

Question 4

Primary cilia have a _____ arrangement.

Answer 4

9x0

Question 5

A basal body:

Answer 5

form the anchors of each cilium.

Responsible for nucleating the cilium.

Question 6

The axoneme

Answer 6

Structural skeleton made from a microtubule rich cylinder. Microtubules are polar polymers and the plus-ends reside at the ciliary tip. In addition to their scaffolding role, axonemes provide the tracks for movement within cilia.

Question 7

The transition zone

Answer 7

links the basal body to the axoneme and to the ciliary membrane.

“gatekeeper” because it limits the diffusion of membrane and soluble proteins into and out of the cilium. ensures that the ciliary membrane is a distinct compartment for cellular signaling.

Question 8

Many proteins of the ______, when absent or defective, are associated with human ciliary diseases (ciliopathies).

Answer 8

transition zone

Question 9

The ciliary membrane is continuous with the

Answer 9

cellular plasma membrane. However, this membrane is compartmentalized (by the transition zone) so that it is a compositionally distinct membrane with unique phospholipids and receptor molecules.

Question 10

What is IFT?

Answer 10

intraflagellar transport (IFT). Transport is bidirectional

Conversely, Both transport mechanisms are required for cilium formation and function.

Question 11

______ direct movement to the ciliary tip (anterograde transport).

Answer 11

kinesin motors (Kinesin-2 family) and the IFT-B protein complex

Question 12

retrograde transport occurs by cytoplasmic _____ motor driven transport with the _____ protein complex.

Answer 12

dynein 2; IFT-A

Question 13

Basal bodies are derived from _____. The _____ centriole forms the basal body.

Answer 13

centrioles; mother

Question 14

When does centriole duplication occur?

Answer 14

G1/S phase boundary coincident with DNA synthesis

Question 15

Ciliogenesis normally occurs during ____ of the cell cycle by assembling from the mother centriole (basal body) of the centriole pair.

Answer 15

G1 (or G0)

distal end of the basal body is capped by a “ciliary vesicle” –> microtubule doublets assemble into vesicle before entire structure fuses with the plasma membrane

Question 16

____ are required for the movement of fluid in the respiratory, neural, and reproductive tracts. Motility is produced by _____.

Answer 16

Motile cilia; axonemal dynein dependent sliding motion between the doublet microtubules of the ciliary axoneme.

Question 17

What is the distinguishing feature between motile and immotile cilia?

Answer 17

the presence of axonemal dynein arms between the doublet microtubules.

Question 18

Reasons for cilia as antennae (4)?

Answer 18

1) concentrates the signal with a high receptor surface to volume ratio
2) the signal is localized and polarized
3) receptors are positioned away from interfering cellular domains (eg negative plasma membrane)
4) cilium can function as a mechanical detector of flow

Question 19

What physical stimuli can cilia sense?

Answer 19

(mechanical strain, temperature, osmolality, and gravity)

Question 20

What chemical stimuli can cilia sense?

Answer 20

(hormones, chemokines, growth factors, and morphogens)

Question 21

Describe the Hedgehog signaling pathway and how cilia are involved.

Answer 21

PTCH1 is the receptor for hedgehog. Presence of PTCH1 in the cilium represses GliA transcription and excludes SMO (smoothened) from the cilium. Binding of Hh to PTCH1 allows SMO to move into cilium and activates GliA at the tip of the cilium. Retrograde transport brings complex out of cilia, presumably to nucleus for transcription.

[smoothened removed from membrane in a vesicle]

Question 22

In what developmental processes is Hedgehog involved?

Answer 22

Bone formation, limb formation, neurogenesis.

Question 23

What other symptoms might someone with situs inversus have?

Answer 23

Chronic sinus infections, pulmonary obstructions.

Question 24

Clinical abnormalities of ciliopathies:

[no need to memorize, just be familiar w/]

Answer 24

• Cystic kidneys
• Nephronophthisis
• Obesity
• Polydactyly
• Retinal degeneration
• Amnosia
• Cancer / Tumorigensis
• Urinary tract malformation
• Cognitive impairment
• Diabetes mellitus
• Infertility
• Occipital meningoencephalocele
• Microphthalmia
• Lung hypoplasia
• Renal hypodysplasia or dysplasia
• Bile-duct dilation
• Postaxial polydactyly
• situs inversus

Question 25

Diseases we have studied that are associated with ciliary malfunction?

Answer 25

VHL, Bardet-Biedl Syndrome (BBS), Auto. Dominant Polycystic Kidney Disease (ADPKD); Auto. Recessive Polycystic Kidney Disease (ARPKD)

Question 26

Bardet-Biedl Syndrome (BBS)

Answer 26

Autosomal recessive disease. Genes encode basal body proteins. 
Symptoms include both neuronal and non-neuronal pathology:
• Photoreceptor degeneration 
• Anosmia 
• Mental retardation / Developmental •
delay
• Neural tube defects •
• Obesity
• Hypogonadism 
• Kidney defects 
• Polydactyly 
• Diabetes
• situs inversus

Question 27

What is anosmia?

Answer 27

Inability to smell.

Question 28

Polycystic Kidney Disease (PKD)

Answer 28

*Polycystins are flow mechanosensor channels that relay Ca++ signals > this, along with other pathways, induces cell proliferation and cystogenesis

[Caused by mutations in polycystin-1 (ADPKD), polycystin-2 (ADPKD), and fibrocystin (ARPKD).]