Cilia and ciliopathies

Question 1

What are basal bodies?

Answer 1

• core anchors from which cilia are formed
• formed from nine triplet microtubules
• polarized structure
• nucleates the cilium

Question 2

What is the axoneme?

Answer 2

• structural skeleton of the cilium
• formed from doublet microtubules
• polar microtubules (alpha and beta tubulin dimers)
• plus-ends reside at the ciliary tips

Question 3

What role does the axoneme have in cilia?

Answer 3

• scaffolding

- provides the tracks for movement within cilia

Question 4

What is the transition zone in cilia?

Answer 4

• links basal body to the axoneme and to the ciliary membrane
• considered the gatekeeper because it limits the diffusion of membrane and soluble proteins in an out of the cilium (distinct compartment within the ciliary membrane)

Question 5

Which proteins in cilia are often associated with human ciliary disease (ciliopathies)?

Answer 5

proteins of the transition zone

Question 6

What is the ciliary membrane?

Answer 6

• continuous with the cellular plasma membrane
• compartmentalized by the transition zone
• compositionally a distinct membrane with unique phospholipids and receptor molecules

Question 7

What is intraflagellar transport?

Answer 7

the mechanism that transports cargo along the axoneme

Question 8

What are the proteins the enable intraflagellar transport?

Answer 8

Kinesin motors - directing movement to the ciliary tip

Dyein motors - retrograde transport (away from ciliary tip)

Question 9

What are the two phases of ciliogenesis?

Answer 9

• centrioles/basal bodies are assembled

- formation of the cilium

Question 10

What are basal bodies derived from?

Answer 10

centrioles (cellular structures that organize the centrosome)
- the older of the two centrioles (mother centriole) functions as the basal body or anchor

Question 11

When does centriole duplication occur?

Answer 11

during the G1 to S phase cell cycle boundary coinciding with DNA synthesis

Question 12

When does ciliogenesis occur?

Answer 12

G1 or G0

Question 13

What starts ciliogenesis?

Answer 13

the distal end of the basal body is capped by a “ciliary vesicle”

Question 14

Is centriole duplication and primary cilia formation tightly linked in multi-ciliated epithelial cells?

Answer 14

basal body assembly is uncoupled from cell cycle and replication is amplified to facilitate multiple basal bodies

Question 15

What are the functions of motile cilia?

Answer 15

• required for the movement of fluid in the respiratory, neural, and reproductive tracts
• most also have sensory function

Question 16

How is motility produced in motile cilia?

Answer 16

axonemal dynein dependent sliding motion between the doublet microtubules of the ciliary axoneme

Question 17

What is the structure of motile cilia?

Answer 17

• distinguishing factor - axonemal dynein arms between the doublet microtubules
• typically have 9 + 2 microtubule arrangement (does not always have central 2 microtubules)

Question 18

What is the structure of sensory or primary cilia?

Answer 18

• 9 + 0 microtubule arrangment

- lack axonemal dynein arms

Question 19

What are some reasons why cilia is used for cell signaling?

Answer 19

• concentrates the signal with a high receptor surface to volume ratio
• signal is localized and polarized within discrete domains of the cell
• receptors are positioned away from interfering cellular domains
• cilium can function as a mechanical detector of flow

Question 20

What stimuli can cilia sense?

Answer 20

physical, light, and chemical stimuli

Question 21

What does the hedgehog signaling pathway require?

Answer 21

cilia

Question 22

What does downstream hedgehog signaling targets facilitate?

Answer 22

• limb formation
• bone formation and homeostasis
• neurogenesis

Question 23

How does the ciliary node establish the left-right asymmetry of the body plan (laterally)?

Answer 23

• ciliary node is an invagination of ciliated cells that forms during gastrulation on the mid plate after anterior-posterior positioning is already established
• nodal cilia possess 9 + 0 and beat in a rotary fashion
• produce net leftward flow of signaling molecules/morphogens
• signals are detected by non-motile sensory cilia and is localized specifically to the future left axis of the body

Question 24

What are the general characteristics of ciliopathies?

Answer 24

• rare
• pleiotropic
• overlapping pho types and genetic mutations
• often affect core cilium structure and function
• diverse number of genes
• genetically complex

Question 25

Bardet-Biedl syndrome

Answer 25

• autosomal recessive
• BBS proteins participate in a protein complex that is required for vesicle transport within the cilium
• causes photoreceptor degeneration, anosmia, mental retardation, neural tube defects, obesity, hypogonadism, kidney defects, diabetes

Question 26

Polycystic kidney disease

Answer 26

autosomal dominant - caused by fibrocystic mutations
autosomal recessive - caused by polycystin-1 and polycystin-2 mutation
- encode channel proteins responsible for calcium signaling
- sense mechanical flow of urine in the kidney lumen to transduce calcium signaling
- renal cysts, liver and pancreas cysts, intracranial aneurysms