Chapter 17: Cytoskeletons

What do cytoskeletons do?

They provide a cell its shape and allows them to organize their internal components, along with the ability to move around

• And usually hide near the plasma membrane

What are intermediate filaments?

They are rope like fibers that extend from nucleus into the cytoplasm and enable cells to withstand mechanical stress

What are intermediate filaments made from?

They are made from fibrous intermediate filament proteins that contain an N-terminal and C-terminal

What does the a-helical region on Intermediate filament protein allow for?

They allow for pairs of intermediate filament proteins to wrap around each other and form a coiled coil dimer 

How are intermediate filaments formed?

1. Two monomers, with their a-helical regions, twist around each other and form a coiled-coil dimer

2. Two coiled-coil dimers then associate with each other to form an staggered, antiparallel tetramer

3. Afterwards, groups of tetramers align with each other side-by-side via lateral, noncovalent interactions and then assemble together to form the final intermediate filament

What are the four different classes of intermediate filaments?

• Keratin filaments

• Vimentin and vimentin-related filaments

• Neuro filaments

• Nuclear laminas

With the first three being found in the cytoplasm and the last being found in the nucleus

What does nuclear lamina do?

It lines the inner face of the nucelar envelope and provides the attachment sites for chromosome

• Additionally, they also disassemble and re-form at each cell division

What does defects in the nuclear lamina cause?

It causes defects in the nuclear envelope that can result in diseases such as progeria, a rare class of premature aging

What does the Kash and SUN domain proteins, located in the perinuclear space, do?

They allow cytoplasmic cytoskeletons to connect to the nuclear lamina or chromosome that are inside the nucleus

What are plectins?

Accessory proteins that strengthens a cell to withstand mechanical stress by linking and bundling intermediate filaments with other cytoskeletal structures

What are microtubules?

They are hollow cylinders that serve as a track for vesicles, organelles, and other macromolecules to be transported through, and help position membrane-enclosed organelles in eukaryotic cells

• Usually have one end attached to a centrosome

What are microtubules made from?

They are made from AB tubulin dimer, consisting of an a-tubulin and B-tubulin subunit

How are microtubules formed?

1. When A-tubulins and B-tubulins bind together through noncovalent bonding, they form a tubulin dimer

2. Multiple tubulin dimers then stack head-to-tail onto each other through non-covalent bonding with a and b tubulins alternating, forming a protofilament

3. Once 13 protofilaments are made, they align side-by-side to form the hollow, cylindrical microtubule structure

What are the a-tubulin and B-tubulin ends on a microtubule called?

B-tubulin ends are called the plus end and the a-tubulin end are called the minus end?

Since each protofilament has structural polarity…

the microtubule will have structural polarity as well

Where do microtubules grow from?

They grow from the y-tubulin ring complex embedded in the centrosome matrix, serving as the starting point for growth

• And allowing Ab tubulin dimers to bind to the plus of a growing microtubule

What does the centrosome matrix organize?

It organizes the location and orientation of microtubule arrays that radiate outward through the cytoplasm

What happens when a tubulin dimer bound to a GTP is added to a growing microtubule?

It’ll cause the addition process of tubulin dimers to occur much faster

What happens when the GTP cap on a microtubule hydrolyzes its GTP into GDP before more tubulin dimers bind?

The GTP cap becomes lost, causing the protofilaments to peel away from the plus end and dimers to be released, resulting in the microtubule shrinking

How do microtubules help neurons?

By transporting organelles, vesicles, and macromolecules through the axon either towards the cell body or towards the nerve terminal

What are the two motor proteins involved with microtubules?

• Kinesin proteins

• Cytoplasmic dynein proteins

With both proteins moving in opposite directions from each other on the microtubule, kinesin moving towards the plus end and dynein moving towards the minus end

What do kinesin and dynein proteins use to move along the microtubule and interact with cargo?

They move along the microtubule using their globular heads and use their tails to interact with cargo, either directly or indirectly through adaptor proteins

How do kinesin and dynein proteins move along the microtubule?

1. when an ATP molecule binds to head 1 and is hydrolyzed into ADP, they detach from the microtubule

2. ADP on head 2 is then exchanged with an ATP molecule, causing a conformational change on head 2 and pulling head 1 forward as a result

How does a cilia sweep fluids across the surface of a cell?

During the power stroke stage, a cilia fully extends itself and sweeps fluids over the surface of the cell and once its finished, it curls back into position during the recovery stroke stage

How does a flagella properl a cell through fluids?

By propagating regular waves along their length in order to propel the attached cell along

What would happen if an isolated doublet were to be exposed to an ATP molecule?

The doublets would slide against each other due to the repetitive action of their associated dyneins

What would happen if a doublet attached to a flagellum are tied to one another by flexible proteins and are exposed to an ATP molecule?

The doublets would bend against each other due to the dynein protein attempting to "walk" along the adjacent microtubule

What are actin filaments?

They are helical polymers of actin proteins, found near the cell peripheral, involved in muscle contraction

• Thinnest out of the 3 filaments

• Highly concentrated in the cell cortex

What are actin filaments made from?

They are made from actin monomers that have a cleft where ATP or ADP are able to bind to

How are actin filaments formed?

1. When ATP-actins bind to a growing strand from the plus end, they hydrolyze their ATP into ADP soon after binding

2. The ADP-actin then remains trapped within the filament until the actin monomer that carries them dissociates from the filament through the minus end, and is repeated again

What is actin treadmilling?

Is the continuous addition of ATP-actins to the plus end and simultaneous dissociation of ADP-actins from the minus end, allowing the filament to maintain its length while the subunits moving through the filament

What are actin-binding proteins?

They are proteins that have the ability to control the behavior of actin filaments in vertebrate cells

What is myosin I?

A motor protein that has a single globular head that can attach to an actin filament and a tail that can attach to another molecule or organelle in the cell

How are Myosin I proteins able to pull the plasma membrane into a new shape?

By binding to an actin filament in the cell cortex

How do polymerizing actin filaments push a plasma membrane forward?

1. When ARP complexes inside the cell use existing actin filaments, they cause the growth of new, branched actin filaments at the cell membrane

2. The growing branch structure then pushes the plasma membrane forward and keeps growing from the plus end until a capping protein binds and stops further growth

What do myosin II proteins consist of?

They consist of two identical heavy chains that each have a globular head and an extended tail that form a single coiled coil tail

What occurs when two myosin II proteins come together?

The proteins coiled-coil tails associate with one another and form a bipolar myosin filament

What do bipolar myosin filaments consist of?

they consist of globular heads projecting outward in opposite directions, with the middle of the filament being the bare region that only has myosin tails

How does the sliding filament mechanism cause muscle contraction?

When a bipolar myosin II filament uses their myosin II heads to walk towards the plus end of two oppositely oriented actin filaments, the actin filaments slide past the myosin and cause muscle contraction

What does the structure of a sarcomere consist of?

It consists of Z discs borders and repeating units of thin actin filaments, bound to the border, and thick myosin filaments overlapping each other, with the relative polarity being the same on either side of the sarcomere midline

What occurs as an actin filament slides over a bipolar myosin II filament?

The sarcomere to which the actin filament belongs to becomes shorter, with the actin filament itself remaining the same length

How does a myosin II protein walk along an actin filament?

1. At the start of the cycle, a myosin II head lacks a bound ATP and is tightly attached to an actin filament

2. An ATP molecule then binds to the "back" of the myosin head, causing a slight conformational change and resulting in the myosin letting go of the actin filament

3. The myosin II head then moves along the actin filament and hydrolyzes its ATP, leaving an ADP and Pi bound to the head

4. Afterwards, the myosin II head binds to a new site on the actin filament and causes the inorganic P to dissociate from the head

5. The myosin II head then contracts forward and returns back to its original conformation, releasing its bound ADP molecule as a result

6. At the end of the cycle, the myosin II head is again tightly attached to the actin filament

What are t-tubules?

They are membrane compartments that are extensions of the sarcolemma and the membrane muscle cell

How is calcium stored in the sarcoplasmic reticulum (SR) and T-tubule membrane released?

When the voltage-gated Ca channel on the t-tubule is opened by an action potential, Ca is released from the t-tubule and causes the Ca-released channel in the SR membrane to open and release calcium as well

How does calcium initiate muscle contraction?

Once Calcium is released from the sarcoplasmic reticulum and T-tubule membrane

1. They bind to the troponin complex on the actin filament and cause complex to undergo conformational change

2. Resulting in the tropomyosin rotating away from the myosin-binding site and allowing for myosin to bind to the site to initiate muscle contraction

How does calcium regulate muscle contraction?

When its present, the myosin binding sites and uncovered and muscle contraction is able to occur, and when its absent, the tropomyosin will block the myosin binding site and prevent muscle contraction from occurring