Cilia and ciliopathies Flashcards
What are basal bodies?
- core anchors from which cilia are formed
- formed from nine triplet microtubules
- polarized structure
- nucleates the cilium
What is the axoneme?
- structural skeleton of the cilium
- formed from doublet microtubules
- polar microtubules (alpha and beta tubulin dimers)
- plus-ends reside at the ciliary tips
What role does the axoneme have in cilia?
- scaffolding
- provides the tracks for movement within cilia
What is the transition zone in cilia?
- 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)
Which proteins in cilia are often associated with human ciliary disease (ciliopathies)?
proteins of the transition zone
What is the ciliary membrane?
- continuous with the cellular plasma membrane
- compartmentalized by the transition zone
- compositionally a distinct membrane with unique phospholipids and receptor molecules
What is intraflagellar transport?
the mechanism that transports cargo along the axoneme
What are the proteins the enable intraflagellar transport?
Kinesin motors - directing movement to the ciliary tip
Dyein motors - retrograde transport (away from ciliary tip)
What are the two phases of ciliogenesis?
- centrioles/basal bodies are assembled
- formation of the cilium
What are basal bodies derived from?
centrioles (cellular structures that organize the centrosome)
- the older of the two centrioles (mother centriole) functions as the basal body or anchor
When does centriole duplication occur?
during the G1 to S phase cell cycle boundary coinciding with DNA synthesis
When does ciliogenesis occur?
G1 or G0
What starts ciliogenesis?
the distal end of the basal body is capped by a “ciliary vesicle”
Is centriole duplication and primary cilia formation tightly linked in multi-ciliated epithelial cells?
basal body assembly is uncoupled from cell cycle and replication is amplified to facilitate multiple basal bodies
What are the functions of motile cilia?
- required for the movement of fluid in the respiratory, neural, and reproductive tracts
- most also have sensory function
How is motility produced in motile cilia?
axonemal dynein dependent sliding motion between the doublet microtubules of the ciliary axoneme
What is the structure of motile cilia?
- distinguishing factor - axonemal dynein arms between the doublet microtubules
- typically have 9 + 2 microtubule arrangement (does not always have central 2 microtubules)
What is the structure of sensory or primary cilia?
- 9 + 0 microtubule arrangment
- lack axonemal dynein arms
What are some reasons why cilia is used for cell signaling?
- 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
What stimuli can cilia sense?
physical, light, and chemical stimuli
What does the hedgehog signaling pathway require?
cilia
What does downstream hedgehog signaling targets facilitate?
- limb formation
- bone formation and homeostasis
- neurogenesis
How does the ciliary node establish the left-right asymmetry of the body plan (laterally)?
- 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
What are the general characteristics of ciliopathies?
- rare
- pleiotropic
- overlapping pho types and genetic mutations
- often affect core cilium structure and function
- diverse number of genes
- genetically complex
Bardet-Biedl syndrome
- 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
Polycystic kidney disease
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
