Cilia

Question 1

Major domains of cilia?

Answer 1

Centriole/basal body: base anchor
Axoneme: scaffold structure
Transition zone: linkage domain
Ciliary membrane: outer sheath
Intraflagellar transport (IFT) machinery

Question 2

Basal body

Answer 2

Core anchor from which cilia are formed. They are MT rich cylinders formed from 9 triplet MT’s (A B C tubules). 9 fold radial symmetry, nec. for beating of motile cilia.
Polarized structure. Formed starting at proximal end. Distal end is responsible for nucleating the cilium.

Question 3

Axoneme

Answer 3

Structural skeleton of cilium. Formed from doublet MT’s (A-B tubules). They assemble from the A and B tubules of the BASAL BODY.
Plus ends at cilia tip.
They also provide tracks for movement (via IFT).

Question 4

Transition zone

Answer 4

Links basal body to axoneme and to the ciliary mem.
Gatekeeper: limits diffusion of membrane and soluble proteins into/out of the cilium.
Ensure ciliary mem is distinct compartment for cellular signaling.
Many proteins of transition zone assoc. w/ ciliopathies.

Question 5

Ciliary mem.

Answer 5

Continuous with plasma m. but compositionally distinct (unique phospholipids/receptors).

Question 6

Intraflagellar transport (IFT)

Answer 6

Cargo nec for assembly/maintenance of cilia and movement of signaling components within the cilium happens through IFT.
Bidirectional with kinesin 2 and IFT-B (towards tip) and dynein 2 and IFT-A (retrograde).
Nec for cilia formation and fx. (Can’t synthesize proteins in cilia)

Question 7

Ciliary assembly, 2 phases

Answer 7

1. ) Centrioles/basal bodies assembled

2. ) Cilium formation

Question 8

Basal/centriole assmbly

Answer 8

Near nucleus, mother centriole has appendages that recruit and are capped by a ciliary vesicle, this is initiating event. 
Basal body (older/mother centriole fx as basal body/anchor), migrate to surface of cell and attach in cytoplasm near the plasma m. Attach to vesicles on the way, fuse with PM. Forms membrane of cilia.

Question 9

Cilium formation

Answer 9

Axonemal doublet MT’s extend from basal body (from near transition zone) to beneath the ciliary mem, forming the cilia.

Question 10

Centrioles

Answer 10

Must also be replicated and segregated (like DNA) in cell division. This is necessary for cilia formation.
2 Fx: organizing MT’s in mitosis and ciliogenesis.

Question 11

Cilia and cell cycle

Answer 11

They form in G1 and disassemble/are resorbed in mitosis. Cells in G0 have NO CILIA.

Question 12

When does centriole duplication happen?

Answer 12

During G1 to S phase boundary coincident with DNA synthesis. MUST occur for ciliogenesis.

Question 13

Which centriole forms cilia?

Answer 13

The mother/older one! In the subsequent G phase.

Question 14

What about terminally differentiated cells with lots of cilia?

Answer 14

Nucleate many cilia per cell.
So need another mechanism for basal body formation, uncoupled from cell cycle and replication amplified to facilitate the multiple basal bodies needed.

Question 15

Motile cilia fx?

Answer 15

Movement and many also have SENSORY fx.

Motility from axonemal dynein dependent sliding motion b/w doublet MT’s of the axoneme.

Question 16

Motile cilia MT arrangement?

Answer 16

Often 9 + 2 (a single pair in middle). But NOT ALL. some can be 9+ 0

Question 17

Non-motile, sensory, primary cilia and MT

Answer 17

9 + 0 MT arrangment, lack axonemal dynein arms, normally perform signaling fx.

Question 18

Cilia and signaling

Answer 18

The cell’s “antenna”.
Used b/c they concentrate signal w/ high receptor surface: volume ratio.
Signal localized/polarized in discrete cell domains.
Receptors are positioned away from interfering cell domains.
Can fx. as mechanical detector of flow

Question 19

Types of signal cilia detect?

Downstream effects?

Answer 19

Physical (mechanical, osmolality, gravity)
Light
chemical (hormones, growth factors etc.).
Effects are many: prolif, motility, growth, polarity, differentiation, tissue maintenance.

Question 20

Hedgehog signaling downstream targets?

Answer 20

This path signals through cilia.
Motile and immotile cilia are imp. for development!
Limb formation, bone formation/homeostasis, neurogenesis.

Question 21

Ciliary node

Answer 21

Establishes L/R asymmetry of the body plane. Ciliary node formed from invagination during gastrulation on midplate.
Nodal cilia: 9+0 organization, beat like rotary. (produces net leftward flow of signaling mlcs/morphogens).
Non-motile sensory cilia are near periphery of the node to signal organogenesis.
This signaling happends on the future left axis of body.

Question 22

Characteristics of ciliopathies?

Answer 22

Rare, pleiotropic (each has diff clinical outcomes), overlapping (most have overlapping phenotypes/genetic mutations), affect structural components of cilia, are diverse (many genes), genetically complex (one gene to many outcomes)

Question 23

Bardet-Biedl Syndrome (BBS)

Answer 23

19 genes mutated! BBS proteins are involved in a protein complex needed for vesicle transport in cilia.
Lots of symptoms, here’s a few: photoreceptor degeneration, mental retardation, obesity, kidney defects, polydactyly

Question 24

Polycystic Kidney Disease (PKD)

Answer 24

AR and AD forms.
AR caused by fibrocystin mutation, AD caused by polycystin mutation.
Genes encode channel proteins for Ca signaling, which sense mechanical flow o urine in kidney lumen to transduce Ca signaling.
Symptoms: cysts in liver pancreas and kidneys, aneurysm.