9.2 Intermediate Filaments Flashcards

1
Q

Why are intermediate filaments known as intermediate filaments?

A

b/c they are larger in diameter and active, but small in microtubule.

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2
Q

What is a difference between microtubules and intermediate filaments?

A

Intermediate filaments form dense networks that run throughout the entire cell. Unlike microtubules the intermediate filament network is not nucleated from a single organizing center.

Unlike microtubules and actin filaments, intermediate filaments perform specialized functions and are not expressed in all organisms or cell types w/in an individual organism

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3
Q

Why do intermediate filaments meet at discreet places at the cell to cell junction?

A

Cells are attaching to each other by forming discreet junction complexes
produced by neighboring cells together. Intermediate filaments support each side of the
complex and give the appearance of running from one cell to the next. Other intermediate
filaments link different regions of individual cell to each other and also support junction attachments between a cell and the surface it is attached to.

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4
Q

When it comes to strength, pulling forces, and compression forces what is the difference between actin filament, microtubules and intermediate filaments?

A

Microtubules resist compression forces very well, but not
pulling forces.

Actin filaments are able to resist more pulling force, but they don’t stretch
much.

Finally intermediates filaments resist a great deal of pulling force and they also
stretch a lot to accommodate that force. They are highly resistant to breaking (this is why they provide mechanical strength to cells)

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5
Q

What is the significance of specialized intermediate filaments?

A

If an individual has a serious mutation in actin or
tubuline it is highly unlikely that the mutation would lead to a viable individual. However
since intermediate filaments are highly specialized and often expressed in a cell type
specific manner a mutation in any one gene for an intermediate filament protein leads to a
defect only in a small number of cell types. As a result these mutations might not be
lethal, but can easily result in clinical disease symptoms

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6
Q

How does the structure of intermediate filaments make them strong?

A

-molecularly strong

-the subunits that make up intermediate filaments are long alpha-helical structures. When these proteins form filaments they do so by forming several protofilaments which are linked together in a
staggered filaments. This means that the ends of the subunits don’t line up across a filament providing a weak spot where the filament can break. There are also many places along an individual subunit where interactions with other subunits form. As a result of all of this intermediate filaments are very strong

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7
Q

What is the molecular explanation for strength in cytoskeleton (actin and microtubule) filaments?

A

actin and microtubules are comprised of globular subunits.

Globular proteins have very limited regions of contact between the individual subunits. Consequently actin filaments and microtubules are broken relatively easily, because the subunits don’t form any interactions between each other.

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8
Q

How do subunits of intermediate filaments look and how are they linked together?

A
  • Individual subunits have globular ends BUT the middle portion of the subunit forms an extended alpha helical region.
  • Two subunits form a dimer in which the alpha helices coil around each other and this structure is known as coiled coil.
  • the subunits that make up the dimer have the same orientation so they are organized in parallel.
  • two intermediate filament dimers form a tetramer, in which Dimers face in the opposite directions.
  • finally the tetramer string together to make what is known as a protofilament. 8 protofilaments are joined to form an individual intermediate filament.
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9
Q

Unlike actin filaments and microtubules, what is unique about the formation of intermediate filaments?

A
  • Intermediate filaments are non-polarized
  • No motor proteins use intermediate filaments
  • no energy is required for the assembly of intermediate filament proteins (no ATP or GTP hydrolisis)

Instead, the assembly or disassembly of intermediate filaments is regulated by the phosphorylation of the subunits.

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10
Q

Why are intermediate filaments non-polarized?

A

because
the most basic subunit is really a tetramer that has one dimer orientated in one direction
and the other dimer oriented in the opposite direction

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11
Q

What is the difference between non-phosphorylated and phosphorylated subunits in intermediate filaments?

A

non-phosphorylated intermediate filament subunits assemble spontaneously

phosphorylation of subunits causes their disassembly or prevents the assembly of these units.

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12
Q

Why can intermediate filaments form bundles w/o proteins?

A

b/c there are many places along the length of an intermediate filament where subunits can laterally interact with each other

ex: neurofilaments

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13
Q

How do intermediate filaments link to other components (not intermediate filaments) of the cell?

A

by a protein called plectin.

Plectin forms a cross bridge linking the intermediate filaments to other structures in the cell such as microtubules.

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14
Q

What does the drug nocodazole do to microtubules and intermediate filaments?

A

Nocodazole causes the destruction of microtubule cytoskeleton which in turn causes the intermediate filament network to collapse

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15
Q

Why do cells have to be dynamic in regard to their position in their cell and their internal arrangement?

A

b/c intermediate filaments still have to change their configuration as the cell changes shape or moves.

ex: as cell moves the intermediate filament network is reorganized

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16
Q

Nuclear intermediate filaments are found where? and what type of component polypeptide?

A

Protein: lamin

location: nuclear lamina (inner lining of nuclear envelope)

17
Q

What is the location and component polypetides of of vimentin-Like intermediate filaments?

A

Polypeptide: Vimentin, Desmin, Glial fibrillary acidic protein (GFAP)

location: cells of mesenchymal origin(fibroblast, bone, blood, muscles, etc)

glial cells (astrocytes and Schwann cells in the NS)

18
Q

Where are epithelial intermediate filaments found? what is the main component polypeptides?

A

Polypeptide: keratins

location: epithelial cells and their derivatives (hair, nails)

19
Q

Where are axonal intermediate filaments located? what is their component polypeptide?

A

polypeptide: neurofilaments
location: neurons

20
Q

What is one clinical application of the diversity of intermediate filaments?

A

the composition of intermediate filaments proteins expressed by tumor cells provide clues to their origin in the body and this has important applications for how a particular cancer should be treated.

21
Q

What do nuclear laminas do? What makes them unique? and how do they behave in when phosphorylated?

A

They provide mechanical strength to the cell nucleus.

Unlike other intermediate filaments, the nuclear lamina form two dimensional structures. The two dimensional mesh work formed by nuclear lamins is consistent in
supporting a two dimensional membrane such as the nuclear envelope.

Phosphorylation of nuclear laminas disasssembles the nuclear envelope during mitosis,

-dephosphorylation causes reassembly at the end of mitosis.

22
Q

What is Desmin?

A

Desmin is a member of the vimentin family of intermediate filament proteins.

23
Q

Where is desmin typically found?

A

typically found in muscle cells where it mechanically links the contractile apparatus of the muscle cells to trans membrane protein complexes and then to the extra cellular matrix.

muscle fibers lack the strength needed to maintain
their structural integrity during contraction.

-Every sacromere contains desmin.

24
Q

What happens if there is a mutation with desmin?

A

Mutations in
desmin and its associated proteins cause a variety of muscle disorders that are sometimes
desmin apathies.

25
Q

What are Glial fibrillary acidic proteins (GFAP)?

A

part of the vimentin like intermediate filaments.

-They are supporting cells of the central and peripheral NS.

These
proteins are expressed in astrocytes which is a cell type found in the central nervous
system. Astrocytes are not neurons instead they are cells that provide mechanical support to neural cells.

26
Q

What happens if there is a mutation in GFAP?

A

Defects in GFAP’s cause a number of neurological disorders such as Alexander disease

27
Q

What is alexander disease?

A

defect in GFAP causes the proteins to form dense masses in brain tissue called Rosenthal fibers. This causes deterioration of brain structures and its replacement with larger fluid filled cavities.

28
Q

What are keratins?

A

Keratins are intermediate filaments that are unique to epithelial cells. Keratins are the
most highly diverse groups and this is consistent with the great diversity types of
epithelial tissues

For example secretory glands, the digestive tract and skin are all lined
with different types of epithelial cells and each express unique keratin intermediate
filament genes.

Even within a specific tissue type more than one type
of keratin can be expressed

29
Q

how does skin gain its mechanical strength to tolerate physical contact with the outside workd?

A

supported by dense bundles of keratin filaments. These bundles of keratin filaments give the cell a prickly or spiny appearance (stratum spinosum)

30
Q

What happens if there are defects in keratin filaments?

A

There are a number of diseases caused by defects in keratin filaments. Some of the most
obvious and dramatic of these are caused by defects in keratins expressed in skin.

Epidermolysis bulosa simple is a horrible condition in which individual skin is easily damaged and forms large blisters.

31
Q

What are neurofilaments?

A

Neurofilaments provide mechanical support to
neuron cell bodies. In addition in some nerve cell types the expression level of neural
filaments determines the size of axonal processes and therefore indirectly influences the speed of nerve impulse transmission.

32
Q

What do defects in neurofilaments cause?

A

nervous system disorders.

One of the
best known is Lou Gehrig’s disease which is also known as amyotrophic lateral sclerosis
or ALS