Lecture 8 - Cell migration and adhesion (MT based) Flashcards
The structure of cilia and flagella is structurally conserved
From single celled organisms to man - many of the same proteins used
So single celled eukaryotes can be used as model organisms for understanding how cilia and flagella work
Each respiratory epithelial cell has how many cilia?
Up to 300
Chalmydomonas reinhardtii is a
Biflagellate green alga
Does ‘breaststroke’
Cilia and Flagella are built from the
Basal body
The flagella is made up of
The basal body
The transition zone
The mature flagellum
The axoneme is
the central strand of a cilium or flagellum
It is composed of an array of microtubules, typically in nine pairs around two single central ones
In the basal body, microtubules are
In nine pairs of triplets, no central MT
In the transition zone, microtubules are
In nine pairs of doublets, no central MT
In the mature axoneme, microtubules are
In nine pairs of doublets, around 2 singlet central MT
The structure of the basal body is the same as
The centriole
In the centrosome there are
Two centrioles, surrounded by PCM
PCM
Pericentriolar material
Gamma tubulin rich
Cytoplasmic MT are nucleated from
The centrosome
9+2 axoneme is
Highly conserved throughout eukaryotic evolution
The basal body is the
MT organising centre
The spindle pole body is the
MT organising centre in yeast and fungi that acts as a centriole equivalent
Centrioles come in
Pairs
MTs are made up of
13 Protofilaments
25nm dia
alpha+beta tubulin
The central pair of MT in the 9+2 axoneme is held in place by
Radial spokes
Nexin connects the
Doublet MT in the outer ring
Important in flagella wave form
The outer doublet MT is made up of the
A + B MTs
Dynein arms are
Molecular motors
Enable flagellum to beat
Proteins are incorporated into the flagellum
At the flagella tip
Proteins are transported into the flagella by
Intraflagellar Transport
Intraflagellar Transport uses
MTs
Intraflagellar transport is
The bi directional movement of particles along the doublet MTs of the flagellar axoneme, between the axoneme and the flagellar membrane
IFT particles are transported to the flagellum +end by
Kinesin II
IFT particles are transported to the flagellum -end by
Dynein 1b
The flagellum -end is located in
The basal body
IFT rafts can be complex assemblies of proteins carried up and down the flagellum - e.g.?
Radial spokes are partially assembled prior to IFT
Cilia and flagella are built by
IFT
IFT forms both
Primary and motile cilia
IFT Kinesin knockout mice embryos
Do not form cilia or flagella
no anterograde transport
IFT Dynein knockout Chlamy mutants
Form bulbous flagellum “Blobs”
no retrograde transport
Centrin is a
Structural protein found in the basal body
Centrin controls
Basal body number
Centrin mutations result in
Too many basal bodies/ too many flagella
known as a vfl mutant (variable flagella no.)
A Chlamy mutant that has only one flagella is called
Uni1
Uni1 mutants
Cannot transition from triplet to doublet microtubules
Results in no flagellum in the daughter basal body
Pf1 mutants have a
Paralysed flagella
Radial spokes do not form correctly
Mbo1 mutants
Move Backwards Only
Mutation in the beak-like projection inside the MT
Swims backwards!
Dyneins
have a tail, head and neck region
The heads contain the ATPase
The head and tail region of the flagella dyneins are anchored to
Two separate MT
Hydrolysis of ATP causes head to move
In flagella, Nexin causes the MT to
BEND, rather than slide against each other
Primary cilia dyskinesia (PCD)
Immotile cilia syndrome
Second most common inherited lung disease after CF
PCD patients have a
Mutation in the 9+2 axoneme
PCD causes
Chronic respiratory disease (respiratory cilia)
Male sterility (sperm flagellum)
Hydrocephalus (ependymal cilia)
The three basic polarity axes are
Anteroposterior
Dorsoventral
Left-right
During embryogenesis
The body axes are specified
What does the node do?
Sets up the left-right axis in vertebrates
What does the node have?
Ciliated cells
What disease results from a lack of cilia in the node?
Situs Inversus
Cilia in the embryonic node
Beat and move morphogens and growth factors to the left
Morphogen
A chemical agent that determines an organism’s shape
Ciliary beating during embryogenesis
Allows aymmetric localisation of growth factors that set up the left right organism polarity
What transcriptiion factor positioned by ciliary beating?
PitX2
Heterotaxy
is partial situs invertus
Situs inversus is seen in 50% patients with
PCD
50% chance of being on the right side