This is the second podcast on the cytoskeleton and here we're going to talk about
centrioles and the microtubule organizing center. Centrioles are of
course the focal point of the microtubule organizing center and these
are paired cylinders, they sit at right angles to each other, they're close to
the nucleus, they are generally partially surrounded by the Golgi and they're
associated with an amorphous peri centriolar material. The pericentriolar
material of course contained the gamma tubulins, the nucleation site from
microtubules plus several hundred associated proteins and centrioles
consist of nine microtubule triplets so you'll often see them designated as nine
plus zero so there are nine outer triplets but no central doublets.
Centrioles are the region where most microtubules are formed. In an interphase
cell, the centrioles control the number, polarity, direction, or orientation and
organization of microtubules in cells that are undergoing division either
mitotic divisions or meiotic divisions. The duplicated microtubule organizing
centers and the centrioles serve as the spindle poles. During interphase, the
minus end of microtubules remains attached to the microtubule organizing
center and the microtubules of the cytoskeleton radiate out towards the
periphery of the cell as the plus end grows towards the plasma membrane.
Centrioles form the basal body which is necessary for the assembly of cilia
because the axoneme in cilia and flagella emanate from the centrioles and
centrioles determine the position of the mitotic and meiotic spindles. This
cartoon just shows the structure of the microtubule organizing center so note
the pair of centrioles and then this cloud of material is just meant to
represent pericentriolar materials
something like 200 different species of proteins associate here but it's also
showing just diagrammatically the rings of gamma tubulins which serve as the
nucleation site for the alpha and beta tubulin dimers and these are growing out
towards the cell periphery so the plus end out here, the minus end attached in
the microtubule organizing center. Now there is a protein that's called nucleus
basal body connector, this protein has not been identified in humans but it has
been identified in other eukaryotic organisms so we don't really understand
its true function but it may somehow anchor the microtubule organizing center
to the nuclear envelope in an interphase cell. We just know from electron
microscopy that in animal cells and actually in all eukaryotic cells the
microtubule organizing center resides near the nucleus. As we've said, basal
bodies form the microtubule organizing center for the tubules for the
microtubule axoneme that would be in cilia so a major function of the
centrioles in interphase cells is the formation of basal bodies and basal
bodies can form de novo without contact of preexisting centrioles. This would be
the so-called acentriolar pathway or basal bodies can form from the
duplication of pre-existing centrioles the so called centriolar pathway. I
don't care that you remember that what I want you to understand though is that in
any epithelium where you have a ciliated epithelium at the base of every single
cilium would be a centriole, the so-called basal body. The micrograph on
the left shows epithelium from the respiratory tract and you can see the
cross-section of the cilia I think you can appreciate the nine plus two for the
ciliary axoneme so the nine microtubule doublets around the
periphery and the central pair of microtubules in the middle for the axoneme,
yet if you look at the basal body, you
don't see the central pair of microtubules but I think you get a sense
that there are nine triplets around the perimeter of the centriole. The
asterisks here are just meant to highlight that there is no central
doublet in the centriole or in the basal body. Here is the mitotic spindle and
remember the primary role of centrioles and the microtubule organizing center
during the cell division cycle is to position the spindle apparatus so here's
the pair of centrioles and we'll talk about this in much greater detail in a
later podcast when we talk about the cell cycle but you can see the various
types of microtubules, the astral microtubules, the kinetochore
microtubules and the polar microtubules. Here's a very nice electron micrograph
showing the outer structure of the centrioles and look at this you can see
the centrioles residing at right angles to each other and here the centriole
pair has replicated so this is probably late in g2 before the mitotic spindle is
assembling itself but I think you can actually count around. If I leave my
arrow here you can look at that and count that as 1 2 3 4 5 6 7 8 9 triplets
and no central doublet. This just shows the centrosome both at the light
microscopic and electron microscopic level. Here the microtubules are stained
with an antibody that's going to fluoresce back green and the microtubule
organizing center is stained with an antibody that's going to fluoresce back
yellow. Here at the electron microscopic level, you might have a cut through this
area, you can see one centriole like this and the other member of the pair here so
they're lying at right angles to each other and the microtubules have just
been colored red in the centrioles and then the individual microtubules
emanating out from the microtubule organizing center have just been colored
as yellow. There are a variety of genetic disorders that are called
ciliopathies and there's one in particular that's called primary ciliary
dyskinesia or Cartagena syndrome that's an immotile cilia syndrome and it
happens to be an autosomal recessive disorder. It occurs about once out of
20,000 births. There's a failure of the mucociliary
transport system in the respiratory epithelium so you prone to respiratory
infections. Males are sterile and females run risks of problems, the sperm tail
flagella axoneme is non-motile cilia and the efferent ductules of the
testes are not functioning. There's a high risk of ectopic pregnancies because
cilia of the oviduct are non-functioning. Some of these patients develop
hydrocephalus because the cilia and the ependymal cells of the brain are not
motile and then about half of the patients you see situs and virtus
because the primary cilium that functions early in embryonic
development that moves some of the transcription factors to the right and
left side of the embryo are also not functioning so you get totally a flip of
how the organs are supposed to be arranged. This primary ciliary dyskinesia,
there's a lack of dynein on the microtubule doublets and that's shown
here. The lack of dynein means that microtubules can't move so the cilia are
inmotile. Here's another example of invasive breast carcinoma this is a
ductile carcinoma so there'd be carcinoma originating from the lactiferous
ducts. Here a histological image of the pathological profile look at these
nuclei are very unusual, they're large. What happens here is you can get multi polar
spindles there's something that breaks down and how the centrioles are going to
divide and in this case is an example of a tri-polar spindle so you're trying to
pull the chromosomes to three different spindle
poles and you might imagine that's going to cause all kinds of problems for the
normal epithelial cells in the breast.