WEEK 6 (Intermediate Filaments) Flashcards

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1
Q

Intermediate Filaments lack polarity (TRUE/FALSE)

A

TRUE

Explanation: Unlike microtubules and microfilaments, intermediate filaments lack polarity and both ends of the filaments are same in nature

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2
Q

Intermediate filaments tend to be less sensitive to ___________________

A

Chemicals

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3
Q

Vimentin is a _______________

A

Intermediate Filament

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4
Q

Epidermolysis bullosa simplex is caused by the deficiency of _______________ polypeptide

A

Keratin

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5
Q

Aggregation of neurofilaments leads to ______________________

A

Neurodegenerative disorders

Explanation: Neurofilaments are intermediate filaments that constitute mature neuronal cells. Aggregation of these neurofilaments blocks axonal transport associated with neurodegenerative disorders

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6
Q

Microfilaments are mostly involved in ___________ processes

A

Motile

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7
Q

Microfilaments are composed of globular subunits of ____________

A

Actin

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8
Q

The identification of actin filaments in a cell can be done by using the protein ______________

A

Myosin

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9
Q

The faster growing end of the microfilament is the plus-end (TRUE/FALSE)

A

TRUE

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10
Q

The drug cytochalasin blocks the __________________

A

Plus-end of microfilaments

(preventing polymerisation there)

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11
Q

Latrunculin blocks the _________________

A

Actin monomers

(prevents their polymerisation)

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12
Q

The head of the myosin binds the _________________________

A

Actin Filament

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13
Q

Titin is the largest protein discovery till date (TRUE/FALSE)

A

TRUE

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14
Q

Which type of cytoskeletal element is described as tough, ropelike fibers composed of a variety of related proteins like Keratin?

A

Intermediate Filaments

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15
Q

What are the functions of the Cytoskeleton?

A
  • Controls cell shape
  • Maintains intracellular organisation
  • Involved in cell movement
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16
Q

What are the properties of Intermediate Filaments?

A
  • Great tensile strength
  • Enable cells to withstand mechanical stress when cells are stretched
  • Toughest & most durable of the cytoskeletal filaments
  • Survive concentrated salt solutions & nonionic detergents
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17
Q

Why are intermediate filaments called “intermediate”

A

In smooth muscle cells where they were first discovered, the diameter was between the thinner actin filaments and thicker myosin filaments

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18
Q

What are the four major classes of Intermediate Filaments?

A
  • Keratin Filaments
  • Vimentin and Vimentin-related filaments
  • Neurofilaments
  • Nuclear lamins
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19
Q

Which intermediate filaments are cytoplasmic?

A
  • Keratin Filaments
  • Vimentin and Vimentin-related filaments
  • Neurofilaments
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20
Q

Which intermediate filament is nuclear?

A

Nuclear lamins

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21
Q

Where are intermediate filaments present in large numbers?

A
  • Nerve cell axons
  • Muscle cells
  • Epithelial cells
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22
Q

What is the difference between central rod domains and terminal domains in different intermediate filaments?

A

CENTRAL ROD DOMAINS = all similar in size and amino acid sequence

TERMINAL DOMAINS = vary greatly in both size and amino acid sequence

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23
Q

Describe the structure of Intermediate filaments

A

Intermediate filament monomer consists of an A-HELICAL CENTRAL ROD DOMAIN with UNSTRUCTURED REGIONS at either end -> Pairs of monomers associate to dorm a DIMER and two dimers line up to form a STAGGERED, ANTIPARALLEL TETRAMER -> Tetramers pack together into a HELICAL ARRAY containing EIGHT TETRAMER STRANDS -> Assemble into a ROPE LIKE INTERMEDIATE FILAMENT

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24
Q

What are Neurofilaments?

A

Intermediate filaments that are found along the axons of vertebrate neurons

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25
Q

What are the functions of Neurofilaments?

A

Provide strength and stability to the long axons that nerve cells use to transmit information

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26
Q

What is Amyotrophic Lateral Sclerosis (ALS)?

A

ALS (also known as LOU GEHRIG’S DISEASE) is a progressive motor neuron disease that is associated with an abnormal accumulation of neurofilaments in cell bodies and axons of motor neurons. It affects movement such as chewing, walking & talking.

RISK FACTORS:
- Most common between 55 & 75
- Males
- Caucasians & Non-hispanics
- Military veterans

SYMPTOMS:
- Axon degeneration
- Muscle weakness
- Muscle Atrophy
- Brain loses its ability to initiate and control voluntary movements

CURE:
There is no cure

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27
Q

What happens in motor neuron disease?

A

As motor neurons degenerate and die, they stop sending messages to the muscles -> the muscles weaken, start to twitch (FASCICULATIONS) and waste away (ATROPHY) -> The brain loses its ability to initiate and control voluntary movements

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28
Q

What are Early symptoms of Amyotrophic Lateral Sclerosis (ALS)?

A
  • Muscle twitches in the arm, leg, shoulder or tongue
  • Muscle cramps
  • Tight and stiff muscles (spaticity)
  • Muscle weakness affecting an arm, a leg, the neck or diaphragm
  • Slurred and nasal speech
  • Difficulty chewing or swallowing
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29
Q

What are Late symptoms of Amyotrophic Lateral Sclerosis (ALS)?

A
  • Dysphagia (chewing & swallowing)
  • Dysarthria (Speaking & forming words)
  • Breathing difficulty/Respiratory failure
  • Anxiety and depression since ALS patients remain able to reason, remember, understand & aware of their progressive loss of function
30
Q

What is the most diverse class of intermediate filament?

A

Keratin

31
Q

What is Epidermolysis bullosa simplex?

A

A rare human genetic disease in which mutations in keratin genes interfere with the formation of keratin filaments in the epidermis. This makes the skin highly vulnerable to mechanical injury so even a gentle pressure can rupture its cells causing the skin to blister.

MUTATIONS:
- KRT5 gene on chromosome 12q
- KRT14 gene on chromosome 17q
- PLEC gene on chromosome 8q

SIGNS & SYMPTOMS:
- Blistering of skin
- Tooth decay
- Deformed/lack of finger & toenails
- Internal blistering in throat, stomach & intestines
- Scalp blistering and loss of hair
- Excessive sweating
- Hardening of the skin on feet or hands
- Thin skin appearance and white bumps
- Difficulty swallowing

32
Q

What is the function of accessory proteins?

A
  • Stabilise and reinforce intermediate filaments
  • Cross-link filaments into bundles
  • Connect filaments to microtubules, actin filaments & adhesive structures in desmosomes
33
Q

What is Plectin?

A

A giant protein found in nearly all mammalian cells which aids in the bundling of intermediate filaments and links these filaments to other cytoskeletal protein networks

34
Q

What do mutations in the gene for plectin cause?

A

A disease that combines features of EPIDERMOLYSIS BULLOSA SIMPLEX, MUSCULAR DYSTROPHY & NEURODEGENERATION

35
Q

What do protein complexes bridge?

A

The nucleus and cytoplasm through the nuclear envelope

36
Q

How is the cytoplasmic skeleton connected across the nuclear envelope to the nuclear lamina/chromosomes?

A

Through sets of linker proteins of the SUN and KASH families -> SUN-DOMAIN PROTEINS interact directly with KASH-DOMAIN PROTEINS to form protein complexes that connect the nucleus to every major cytoskeleton network

37
Q

What are the other functions of SUN-KASH proteins?

A
  • Required for attaching CENTROSOMES to the NUCLEAR PERIPHERY
  • Alignment of homologous chromosomes, their pairing and recombination in meiosis
38
Q

What is Duchenne Muscular Dystrophy?

A

A progressive form of muscular dystrophy that occurs primarily in males and is the most common type of severe hereditary myopathies (Skeletal muscle disorder). Incurable recessive X-linked disease.

CAUSE:
Mutation in DMD gene that codes for DYSTROPHIN. Dystrophin is a critical part of the DYSTROPHIN-GLYCOPROTEIN COMPLEX (DGC) which plays an important role as a structural unit of muscle. In DMD, both DYSTROPHIN and DGC proteins are missing which leads to necrosis of muscle cells.
[FATAL - death by lung or heart tissues caused by it]

39
Q

What is the function of Intermediate Filaments of the nuclear lamina?

A
  • Line the inner face of the nuclear envelope
  • Provide attachment sites for the chromosomes
40
Q

What is Hutchinson-Gilford Progeria Syndrome (HGPS)?

A

A disease caused by defects in nuclear lamin which cause premature aging

CAUSE:
Mutations in LMNA gene on chromosome 1. The LMNA gene provides instructions for making LAMIN A which is a protein that plays an important role in determining the shape of the nucleus within cells. The body makes an ABNORMAL FORM of lamin A called PROGERIN which leads to rapid ageing.

SYMPTOMS:
- Wrinkled skin
- Lose teeth & hair
- Severe cardiovascular disease

41
Q

What are some functions of Actin Filaments?

A
  • Microvilli
  • Contractile bundles in the cytoplasm
  • Finger-like protrusions
  • Contractile ring during cell division
42
Q

What are the properties of Actin Filaments?

A
  • Essential for many of the cell’s movements
  • Unstable but by associating with other proteins can form stable structures in cells
43
Q

What are the properties of Actin Filaments?

A
  • Essential for many of the cell’s movements
  • Unstable but by associating with other proteins can form stable structures in cells
44
Q

Describe the structure of an Actin Filament

A
  • Subunit of each actin filament is an actin monomer
  • A cleft in the monomer provides a binding site for ATP/ADP
  • Two-stranded helix with a twist repeating every 37nm
45
Q

Describe how ATP hydrolysis decreases the stability of the actin polymer

A

Actin monomers in the cytosol carry ATP which is hydrolysed to ADP soon after assembly into a growing filament -> ATP hydrolysis decreases the stability of the actin polymer -> The ADP molecules remain trapped within the actin filament, unable to exchange with ATP until the actin monomer that carries them dissociates from the filament

46
Q

What happens when the rates of addition and loss are equal in actin?

A

The filament stays the same length although individual actin monomers move through the filament from the plus to the minus end

47
Q

What does the drug Phalloidin do?

A

Binds and stabilises filaments

48
Q

Why are Latrunculins produced for fundamental research?

A

They have potential medical applications since they show antiproliferative, antimicrobial and antimetastatic activities

49
Q

Where are the other actin molecules that aren’t assembled into filaments?

A

Remains as actin monomers in the cytosol

50
Q

What is the function of Thymosin and Profilin?

A

Bind to actin monomers in the cytosol preventing them from adding to the ends of actin filaments. They play a crucial role in regulating actin polymerisation.

51
Q

What happens when actin filaments are needed?

A

Actin-binding proteins such as Formin and Actin-related proteins promote actin polymerisation

52
Q

What is the Cell cortex?

A

Where actin is highly concentrated in a layer just under the plasma membrane. Actin filaments are linked by actin-binding proteins into a meshwork that supports the plasma membrane and gives it mechanical strength.

53
Q

Describe the cell cortex of a red blood cell

A

Spectrin dimers are linked end-to-end to form longer tetramers -> Spectrin tetramers with a smaller number of actin molecules are linked together into a mesh -> This network is attached to the plasma membrane by binding of at least two types of attachment proteins to two kinds of transmembrane proteins

54
Q

Describe how forces generated in the actin-filament-rich cortex help move a cell forward

A

1) Actin polymerisation at plus end protrudes lammelipodium
2) Protrusions adhere to the surface over which myosin motor proteins slide along actin filaments
3) Further protrusion moves it forwards

55
Q

What are the properties of Filopodia?

A
  • Thin, stiff protrusions
  • Help the cell to probe its environment and find the correct path to its target cell
56
Q

What do Lamellipodia and Filopodia have in common?

A
  • Exploratory, motile structures that form and retract with great speed
  • Generated by the rapid, local growth of actin filaments
    [which assemble close to the plasma membrane and elongate by the addition of actin monomers at their plus ends]
57
Q

What is Myosin?

A

An actin-binding protein that belongs to a family of motor proteins that bind to and hydrolyse ATP which provides the energy for their movement along actin filaments toward the plus end

58
Q

What are the properties of Myosin-I?

A
  • Simplest myosin
  • Binds to actin filament in cell cortex pulling the plasma membrane into a new shape
  • Single globular head that attaches to an actin filament & a tail that attaches to another molecule or organelle in the cell
    [arrangement allows the head domain to move a vesicle relative to an actin filament]
59
Q

What are the properties of Myosin-II?

A
  • Muscle myosin
  • Dimers with two globular ATP heads at one end and an extended tail
  • Can associate with one another to form MYOSIN FILAMENTS in which the heads project outward from the middle in opposite directions
60
Q

What happens when one myosin head releases the actin filament to reposition itself?

A

Other myosin must remain attached so the structure does not fall apart

61
Q

What are Skeletal muscle fibers?

A

Huge, multinucleate individual cells formed by the fusion of many separate smaller cells

62
Q

What does a myofibril consist of?

A

A chain of identical tiny contractile units called sarcomeres

63
Q

What are sarcomeres?

A

Contractile units of muscle and are highly organised assemblies of actin filaments and myosin filaments composed of a muscle-specific form of myosin-II

64
Q

What happens during muscle contraction?

A

Actin and myosin filaments slide past each other -> Filaments remain the same length but the sarcomere to which they belong shortens -> Sliding motion is driven by the myosin heads walking towards the plus ends of the adjacent actin filaments

65
Q

Describe the stages leading to muscle contraction

A

1) Neurotransmitter released from the nerve terminal triggers an action potential in the muscle cell plasma membrane
2) Electrical excitation spreads into T tubules that extend inward from the plasma membrane around each myofibril
3) Electrical signal is relayed to the sarcoplasmic reticulum
4) Sarcoplasmic reticulum contains a very high concentration of Ca2+ which in response to electrical excitation is released into the cytosol

66
Q

What is the Sarcoplasmic reticulum?

A

A specialised region of the endoplasmic reticulum which is an adjacent sheath of interconnected flattened vesicles that surrounds each myofibril like a net stocking

67
Q

Activation of Rho family GTPases have a dramatic effect on what?

A

The organisation of actin filaments in fibroblasts

68
Q

What are Kinesins and Dyneins?

A

Microtubule-associated motor proteins that use the energy of ATP hydrolysis to move unidirectionally along microtubules. They carry specific organelles, vesicles and other types of cargo to particular locations in the cell.

69
Q

What is the rhythmic beating of eukaryotic cilia and flagella caused by?

A

Bending of the microtubules driven by the ciliary dynein motor protein

70
Q

Actin filaments are more flexible than microtubules (TRUE/FALSE)

A

TRUE