Lecture 15: Cytoskeleton in Disease Flashcards
what are Rho GTPases
molecular switch that control actin dynamics
what are Rac1 and Cdc42
members of the Rho GTPase family
invovled in the formation of lamellipodium and filopodia which is a protrusion which moves the cell
they activate downstream effector proteins which promote the formation of actin filaments and reorginsation of the actin cytoskeleton
what is gastrulation
key process in embryonic development that involves the formation of the 3 germ layers - mesoderm, endoderm, and ectoderm
what is the signal pathway involved in gastrulation
Wnt
what is Wnt essential for
for the formation of the dorsal ventral axis which establishes the back and belly of the embryo - the neural tube which the precursor to the CNS
what are BMP and FGF involved in
specifying the anterior-posterior axis - head and tail
specifying left-right axis - orientation of internal organs
what is the role of the cytoskeleton in cell differentiation
gene expression
cell fate determination
what do actin filaments help maintain in the nucleus
shape and stiffness
what do microtubules provide for the nucleus
provides tracks for the movement of nucleus along the cytoskeleton
how does the cytoskeleton regulate transcription factor activity
YAP - yes associated protein- is regulated by actin cytoskeleton as YAP is activated by changes in cell shape and tension
what is progeria
a premature aging disorder which is caused by defects in the nuclear lamin- nuclear instability leads to impaired cell death, increased cell death etc
what are Purkinje neurons
type of neuron found in cerebellum which controls motor control, balance and coordination
how is the cytoskeleton involved with Purkinje neurons
involved in the migration of Purkinje neuron precursors to the cerebellar plate, the establishment of dendritic arbors and formation of axons and synapses
what is lissencephaly
smooth brain - caused by a mutation in reelin gene
what is microcephaly
small head size and underdeveloped brain - abnormal spindle-like microcephaly associated protein (ASPM) plays a role in mitotic spindle function
what do mutations in ASPM cause
abnormal spindle formation
defective xsome segregation
altered cell cycle progression
ASPM is required for symmetrical division
what is the role of ASPM in neuronal development
ensures neural progenitor cells divide correctly and that genetic material is evenly distributed to two daughter cells
orientation of the mitotic spindle in neurons- horizontal= few neurons = small brain
vertical = more neurons = larger brain
how is Parkinsons and the cytoskeleton linked
alpha -synuclein is involved in Parkinsons
alpha- synuclein can bind to microtubules and actin filaments - which disrupts the normal function of the cytoskeleton
what is the treatment for alpha-synuclein
RNA inteference RNAi target and degrade messenger RNA that encodes alpha-synuclein
antibodies
explain the cytoskeleton and tumourgenesis
tumours contain cells with centrosome abnormalities
what is the epithelial mesenchymal transition (EMT)
epithelial cells lose their polarity and cell-cell contacts and acquire mesenchymal characteristics
how does the cytoskelton affect the EMT
regulates cell shape, motility and signalling
regulation of the signalling pathways that are important for EMT
Rho pathway involved in regulation of actin dynamics
what happens during EMT and cytoskeleton dysfunction
cortical actin network is disrupted = formation of stress fibers that promote cell motility and invasiveness
what are taxanes
semi-synthetic chemotherapies derived from the Yew tree
inhibit depolymerisation of microtubule during mitosis
what is colchicine
chemotherapy drug that targets microtubules by binding to tubulin and preventing microtubule polymerisation
from the autumn crocus flower
however causes vomitting, marrow suppression, neuropathy
what are vinca alkaloids
extracted from periwinkle
inhibit microtubule formation
administered intravenously
metabolised in liver
