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Flashcards in Cilia Deck (24):

Major domains of cilia?

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


Basal body

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.



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).


Transition zone

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.


Ciliary mem.

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


Intraflagellar transport (IFT)

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)


Ciliary assembly, 2 phases

1.) Centrioles/basal bodies assembled
2.) Cilium formation


Basal/centriole assmbly

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.


Cilium formation

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



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.


Cilia and cell cycle

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


When does centriole duplication happen?

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


Which centriole forms cilia?

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


What about terminally differentiated cells with lots of cilia?

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.


Motile cilia fx?

Movement and many also have SENSORY fx.
Motility from axonemal dynein dependent sliding motion b/w doublet MT's of the axoneme.


Motile cilia MT arrangement?

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


Non-motile, sensory, primary cilia and MT

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


Cilia and signaling

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


Types of signal cilia detect?
Downstream effects?

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


Hedgehog signaling downstream targets?

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


Ciliary node

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.


Characteristics of ciliopathies?

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)


Bardet-Biedl Syndrome (BBS)

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


Polycystic Kidney Disease (PKD)

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.