Cilia and ciliopathies Yo Flashcards
5 Components of cilia
- Basal body: base anchor
- Axoneme: scaffold structure
- Transition zone: linkage domain
- Intraflagellar transport: transporters
- Ciliary membrane: outer sheath
Basal body
function?
Structure?
base anchor from which cilia are formed
-microtubule rich cylinder structure formed from 9 triplet microtubules
Axoneme
function?
Structure?
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
Transition zone
- 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.
Intraflagellar transport
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)
Ciliary membrane
continuous with plasma membrane but is compartamentalized by transition zone
–> compositionally distinct membrane with unique phospholipids n receptor molecules
How are cilia assembled (ciliogenesis)
By centriole formation and cilium formation:
- Centriole dup. occurs during G1 to S-phase
- one older “maternal centriole” and 1 young
- Centrioles assemble/pair
- Distal end of basal body is capped
by “ciliary vesicle” - Microtubule doublets assemble into ciliary vesicle
- Entire structure fuses with PM
Motile Cilia
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)
Sensory Cilia
aka Non-motile aka primary cilia
have signalling function
- lack axonemal dynein arms
- have a 9+0 microtubule arrangement
Why are cilia used for signaling?
Cilia are the cell’s antennae
allows for:
- Concentration of signal
- localization of signal
- polarizing signal
- fluid mechanics
- charge disruption
- flow sensing by mechanical bending
These produce downstream events
Downstream events of cilia signaling
- Cellular proliferation
- cellular motility
- polarity
- growth
- differentiation
- tissue maintenence
Signaling pathways that function through cilia
- Hedgehog (Hh) signaling pathway
- Activation/Repression of Hh paracrine signaling pathway (Gli transcriptional activator)
- Wnt, PDGF, FGF
Examples of how cilia function in development and homeostasis
Motile and immotile cilia are important.
- limb formation
- bone formation and homeostasis
- neurogenesis
- polarity
- neural tube formation
AND MUCH MUCH MORE IM NOT WRITING
Characteristics of cilial syndromes
- cystic kidneys
- nephronophthisis
Many more that can affect along process of cilia formation.
Clinical features / defects associated with ciliopathies
- Rare.
- Pleiotropic.
- Each ciliopathy is characterized by different clinical outcomes. - Overlapping.
- Most of the ciliopathies have overlapping phenotypes and genetic
mutations. - Structural.
- Mutations often affect core cilium structure and function. - Diverse.
- ~50 genes are known to be mutated in ciliopathies to date. - Genetically complex.
- Mutations in the same gene (Cep290) can produce four
different clinical outcomes
