Cilia Flashcards
components of cilia
centriole/basal body, axoneme, transition zone, ciliary membrane, and intraflagellar transport
basal body
core anchors of cilia, microtubule rich cylinder shaped structres formed from 9 triplet microtubules (A-B-C-tubules)m 150-200 nm in diameter and 500 nm in length, formed from proximal end, distal end responsible for nucleating cilium
axoneme
structual skeleton of cilium, form from A- and B-tubules (doublet microtubules) assembled from basal body. Plus-ends of MTs reside at ciliary tip, length varies from 1micro to 10s od microns, also provice the tracks for movement within cilia.
transition zone
links basal body to axoneme and to ciliary membrane, limits diffusion of membrane and soluble proteins into and out of the cilium, ensures ciliary membrane is distant compartment for cellular signaling, ciliopathies arise from this zone
ciliary membrane
continuous with plasma membrane, compartmentalized, compositionally distict membrane with unique phospholipids and receptor molecules
infraflagellar transport
transports cargo along axoneme important for assembly and maintenance of cilium and for the movement of signaling components within the cilium. Bidirectional with kinesin motors (Kinesin-2 family) and the IFT-B protein complex directing movement to the ciliary tip (anterograde transport). dynein 2 motor also used with IFT-A protein complex.
ciliogenesis
occurs during G1 though uncoupled from cell cylcle, 2 phases: 1)basal bodies assembled from centrioles (organize centrosome), older centriole functions as casal body anchor (duplication bewtween G1/s-phase). 2) formation of cilium. All begins w/ distal end of basal body is caped, MT doublets assemble onto ciliary vesicle (cap) before fusion to membrane.
motile cilia
can do sensory as well, required for movement of fluid in respiratory, neural, and reproductive tracts, motion produced by axonemal and dynein dependent sliding motion between doublet MTs (distinguishing factor). Have 9 doublet MRs around central pair of singlet MTs (9+2)
sensory cilia
9+0 MT arrangement and lack axonemal gynein arms. Perform signaling functions
cilia in signaling pathway
concentrates signal with high receptor surface to volume ratio, signal localized and polarized, can sense physical stimuli, light and chemical stimuli. Hedgehog (Hh) pathway is well established. Activation/repression of Hh paracrine pathway (Glioma tumor or Gli transcriotional activator) requires cilia. Wnt, PDGF, FGF and others use cilia
cilia function
limb formation, bone formation and homeostasis, neurogenesis, tubule formation, renal formation, laterality, eye formation. Ciliary node responsible for laterality, forms as invagination during gastrulation, 9+0, 600 rpm to make net leftward flow of signals.
ciliopathies and clinical abnormalities
cystic kidneys, nephronophthisis, obesity, polydactyly, retinal degeneration, Amnosia, Cancer, urinary tract malformation, cognitive impairment, diabetes mellitus, Infertility, Occipital meningocephalocele, microphthalmia, lung hypoplasia, renal hypo/dysplasia, bile-duct dilatarion, situs inversus
Bardet-Biedl Syndrome
Autosomal recessive, 15 mutations can cause, BBS proteins participate in protein complex required for vasicle transport within the cilium, symptoms: photoreceptor degeneration, Anosmia, mental retardation/ developmental delay, neural tube defects, obesity, hypogonadism, kidney defects, polydactyly, diabetes, situs inversus
polycystic kidney disease (PKD)
dominant: mutation in polycystin-1 and -2 (PKD1 and 2) 1:1000. recessive: mutation in fibrocystin 1:20000. control channels for Ca signaling, normally sense mechanical flow of urine in kidney lumen to transduce Ca signaling. Symptoms: Renal cysts, liver and pancreas cysts, Intracranial aneurysms
