Lecture 15: Cytoskeleton in Disease

Question 1

what are Rho GTPases

Answer 1

molecular switch that control actin dynamics

Question 2

what are Rac1 and Cdc42

Answer 2

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

Question 3

what is gastrulation

Answer 3

key process in embryonic development that involves the formation of the 3 germ layers - mesoderm, endoderm, and ectoderm

Question 4

what is the signal pathway involved in gastrulation

Answer 4

Wnt

Question 5

what is Wnt essential for

Answer 5

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

Question 6

what are BMP and FGF involved in

Answer 6

specifying the anterior-posterior axis - head and tail
specifying left-right axis - orientation of internal organs

Question 7

what is the role of the cytoskeleton in cell differentiation

Answer 7

gene expression
cell fate determination

Question 8

what do actin filaments help maintain in the nucleus

Answer 8

shape and stiffness

Question 9

what do microtubules provide for the nucleus

Answer 9

provides tracks for the movement of nucleus along the cytoskeleton

Question 10

how does the cytoskeleton regulate transcription factor activity

Answer 10

YAP - yes associated protein- is regulated by actin cytoskeleton as YAP is activated by changes in cell shape and tension

Question 11

what is progeria

Answer 11

a premature aging disorder which is caused by defects in the nuclear lamin- nuclear instability leads to impaired cell death, increased cell death etc

Question 12

what are Purkinje neurons

Answer 12

type of neuron found in cerebellum which controls motor control, balance and coordination

Question 13

how is the cytoskeleton involved with Purkinje neurons

Answer 13

involved in the migration of Purkinje neuron precursors to the cerebellar plate, the establishment of dendritic arbors and formation of axons and synapses

Question 14

what is lissencephaly

Answer 14

smooth brain - caused by a mutation in reelin gene

Question 15

what is microcephaly

Answer 15

small head size and underdeveloped brain - abnormal spindle-like microcephaly associated protein (ASPM) plays a role in mitotic spindle function

Question 16

what do mutations in ASPM cause

Answer 16

abnormal spindle formation
defective xsome segregation
altered cell cycle progression
ASPM is required for symmetrical division

Question 17

what is the role of ASPM in neuronal development

Answer 17

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

Question 18

how is Parkinsons and the cytoskeleton linked

Answer 18

alpha -synuclein is involved in Parkinsons
alpha- synuclein can bind to microtubules and actin filaments - which disrupts the normal function of the cytoskeleton

Question 19

what is the treatment for alpha-synuclein

Answer 19

RNA inteference RNAi target and degrade messenger RNA that encodes alpha-synuclein
antibodies

Question 20

explain the cytoskeleton and tumourgenesis

Answer 20

tumours contain cells with centrosome abnormalities

Question 21

what is the epithelial mesenchymal transition (EMT)

Answer 21

epithelial cells lose their polarity and cell-cell contacts and acquire mesenchymal characteristics

Question 22

how does the cytoskelton affect the EMT

Answer 22

regulates cell shape, motility and signalling
regulation of the signalling pathways that are important for EMT
Rho pathway involved in regulation of actin dynamics

Question 23

what happens during EMT and cytoskeleton dysfunction

Answer 23

cortical actin network is disrupted = formation of stress fibers that promote cell motility and invasiveness

Question 24

what are taxanes

Answer 24

semi-synthetic chemotherapies derived from the Yew tree
inhibit depolymerisation of microtubule during mitosis

Question 25

what is colchicine

Answer 25

chemotherapy drug that targets microtubules by binding to tubulin and preventing microtubule polymerisation
from the autumn crocus flower
however causes vomitting, marrow suppression, neuropathy

Question 26

what are vinca alkaloids

Answer 26

extracted from periwinkle
inhibit microtubule formation
administered intravenously
metabolised in liver