Flashcards in Cilia Deck (28)
1. Identify the components of cilia.
2. Explain how cilia are assembled.
3. Explain the differences between motile and sensory cilia.
4. Identify signaling pathways that function through cilia and explain why cilia are used for signaling.
5. Provide examples of how cilia function in development and tissue homeostasis.
6. Recognize the clinical features and cilia defects associated with ciliopathies.
The basal body is composed of _____, the axoneme composed of_____.
triplet radial microtubule repeats; double radial microtubule repeats
Motile cilia have _____ and are arranged in a _____.
dynein arms; 9x2
Primary cilia have a _____ arrangement.
A basal body:
form the anchors of each cilium.
Responsible for nucleating the cilium.
Structural skeleton made from a microtubule rich cylinder. Microtubules are polar polymers and the plus-ends reside at the ciliary tip. In addition to their scaffolding role, axonemes provide the tracks for movement within cilia.
The transition zone
links the basal body to the axoneme and to the ciliary membrane.
“gatekeeper” because it limits the diffusion of membrane and soluble proteins into and out of the cilium. ensures that the ciliary membrane is a distinct compartment for cellular signaling.
Many proteins of the ______, when absent or defective, are associated with human ciliary diseases (ciliopathies).
The ciliary membrane is continuous with the
cellular plasma membrane. However, this membrane is compartmentalized (by the transition zone) so that it is a compositionally distinct membrane with unique phospholipids and receptor molecules.
What is IFT?
intraflagellar transport (IFT). Transport is bidirectional
Conversely, Both transport mechanisms are required for cilium formation and function.
______ direct movement to the ciliary tip (anterograde transport).
kinesin motors (Kinesin-2 family) and the IFT-B protein complex
retrograde transport occurs by cytoplasmic _____ motor driven transport with the _____ protein complex.
dynein 2; IFT-A
Basal bodies are derived from _____. The _____ centriole forms the basal body.
When does centriole duplication occur?
G1/S phase boundary coincident with DNA synthesis
Ciliogenesis normally occurs during ____ of the cell cycle by assembling from the mother centriole (basal body) of the centriole pair.
G1 (or G0)
distal end of the basal body is capped by a "ciliary vesicle" --> microtubule doublets assemble into vesicle before entire structure fuses with the plasma membrane
____ are required for the movement of fluid in the respiratory, neural, and reproductive tracts. Motility is produced by _____.
Motile cilia; axonemal dynein dependent sliding motion between the doublet microtubules of the ciliary axoneme.
What is the distinguishing feature between motile and immotile cilia?
the presence of axonemal dynein arms between the doublet microtubules.
Reasons for cilia as antennae (4)?
1) concentrates the signal with a high receptor surface to volume ratio
2) the signal is localized and polarized
3) receptors are positioned away from interfering cellular domains (eg negative plasma membrane)
4) cilium can function as a mechanical detector of flow
What physical stimuli can cilia sense?
(mechanical strain, temperature, osmolality, and gravity)
What chemical stimuli can cilia sense?
(hormones, chemokines, growth factors, and morphogens)
Describe the Hedgehog signaling pathway and how cilia are involved.
PTCH1 is the receptor for hedgehog. Presence of PTCH1 in the cilium represses GliA transcription and excludes SMO (smoothened) from the cilium. Binding of Hh to PTCH1 allows SMO to move into cilium and activates GliA at the tip of the cilium. Retrograde transport brings complex out of cilia, presumably to nucleus for transcription.
[smoothened removed from membrane in a vesicle]
In what developmental processes is Hedgehog involved?
Bone formation, limb formation, neurogenesis.
What other symptoms might someone with situs inversus have?
Chronic sinus infections, pulmonary obstructions.
Clinical abnormalities of ciliopathies:
[no need to memorize, just be familiar w/]
• Cystic kidneys
• Retinal degeneration
• Cancer / Tumorigensis
• Urinary tract malformation
• Cognitive impairment
• Diabetes mellitus
• Occipital meningoencephalocele
• Lung hypoplasia
• Renal hypodysplasia or dysplasia
• Bile-duct dilation
• Postaxial polydactyly
• situs inversus
Diseases we have studied that are associated with ciliary malfunction?
VHL, Bardet-Biedl Syndrome (BBS), Auto. Dominant Polycystic Kidney Disease (ADPKD); Auto. Recessive Polycystic Kidney Disease (ARPKD)
Bardet-Biedl Syndrome (BBS)
Autosomal recessive disease. Genes encode basal body proteins.
Symptoms include both neuronal and non-neuronal pathology:
• Photoreceptor degeneration
• Mental retardation / Developmental •
• Neural tube defects •
• Kidney defects
• situs inversus
What is anosmia?
Inability to smell.