Week 9 (Cell Migration and division)

Question 1

What is Cell migration?

Answer 1

is a central process in the development and maintenance of multicellular organisms. Tissue formation during embryonic development, wound healing, angiogenesis (new blood vessel formation) and immune responses all require the orchestrated movement of cells in particular directions to specific locations.

Question 2

What is metastasis?

Answer 2

During pathological conditions, uncontrolled highly migratory cells are the main cause of tumour invasion and metastasis (tumour cells migrating and growing in distant sites).

Question 3

Cells can migrate individually or

Answer 3

in a sheet

Question 4

What are the three major components of the cytoskeleton?

Answer 4

Actin filaments
Microtubules (made of the protein tubulin)
Intermediate filaments, which have more than 60 different building block proteins, have been found so far only in animal cells (apart from one non-eukaryotic bacterial intermediate filament crescentin)

Question 5

What are the Components of a cytoskeleton?

Answer 5

• Microtubules
• Intermediate filaments
• Actin filaments

Question 6

What is myosin?

Answer 6

It is the prototype of a molecular motor—a protein that converts chemical energy in the form of ATP to mechanical energy, thus generating force and together with Actin drives movement.

Question 7

Most myosin molecules are composed of

Answer 7

• Head: in charge of binding to actin filaments, hydrolysing ATP to generate force, moving long actin filament
• Neck: acting as a linker and as a lever arm for transducing force produced by the catalytic motor domain, serving as a binding site for myosin light chain
• Tail: mediating interaction with cargo molecules and/or other myosin subunits

Question 8

Actin-Myosin interaction in cell contraction: Attached

Answer 8

• At the start of cycle showing this figure, a myosin head lacking a bound nucleotide is locked tightly onto an actin filament in a rigor configuration.
• In an actively contracting muscle this state is very short lived, being rapidly terminated by the binding of a molecule of ATP

Question 9

Actin-Myosin interaction in cell contraction: Released

Answer 9

• A molecule of ATP binds to the large cleft on the back of the head and immediately causes a slight change in the conformation of the domains that make up the actin-binding site.
• This reduces the affinity of the head for actin and allows it to move along the filament.

Question 10

Actin-Myosin interaction in cell contraction: Cocked

Answer 10

• The cleft closes like a clam shell around the ATP molecule, triggering a large shape change that caused the heard to be displaced along the filament by a distance of about 5nm.
• Hydrolysis of ATP occurs, but the ADP and Pi produced remain tightly bound to the protein.

Question 11

Actin-Myosin interaction in cell contraction: Force-generating

Answer 11

• The weak binding of the myosin head to a new site on the act filament causes release of the inorganic phosphate produced by ATP hydrolysis, concomitantly with the tight binding of the head to actin.
• This release triggers the power stroke-the force-generating change in shape during which the head regains its original conformation. In the course of the power stroke, the head loses its bound ADP, thereby returning to the start of the cycle ‘Attached’.

Question 12

What are the Important structures involved in cell migration?

Answer 12

1. Filopodia
2. Lamellipodium
3. Focal Adhesions
4. Cortex
5. Transverse Arcs

Question 13

Describe the properties of filopodia

Answer 13

Thin, spike-like protrusion with an actin filament core, essentially one-dimensional

Question 14

Describe the properties of lamellipodium

Answer 14

Two-dimensional sheet-like structures, containing a cross-linked mesh of actin filaments

Question 15

What is the function of Focal adhesions?

Name one of the major components of focal adhesions

Answer 15

• The major contact points between the cell and its substratum. They are large macromolecular assemblies through which mechanical force and regulatory signals are transmitted between the extracellular matrix (ECM) and an interacting cell.
• Integrins are one of the major components in focal adhesion, together with some adaptor proteins such as vinculin, talin and paxillin.

Question 16

What is Focal adhesion kinase (FAK)?

Answer 16

A focal adhesion-associated protein kinase involved in cellular adhesion, spreading and migration.

Question 17

What does FAK bind to?

What does this initiate?

Answer 17

FAK binds to the cytosolic tail of integrin subunits with the assistance of other proteins and functions as a kinase to initiate the intracellular signalling cascade.

Question 18

Actin Arrays: Ventral stress fibres

Answer 18

Associate with focal adhesions at both ends, located on the ventral surface of the cell, and function in adhesion and contraction

Question 19

Actin Arrays: Transverse arcs

Answer 19

Not directly linked to focal adhesions, and typically flow from the leading edge of the cell, back towards the cell centre

Question 20

Actin Arrays: Dorsal stress fibres

Answer 20

Located at the trailing edge of the cell, attach to focal adhesions on the ventral surface of the trailing edge, and extend dorsally, towards the cell centre to attach to transverse arcs

Question 21

What does cell migration require?

Answer 21

the polarization and the interaction between the cells and the extracellular matrix. During migration cells will be polarized into a leading edge and trailing edge.

Question 22

What does the leading edge of a migrating cell contain?

Answer 22

The leading edge of a migrating cell is broader and contains lamellipodia and/or filopodia

Question 23

What happens at the trailing edge?

Answer 23

The trailing edge is called the trail and is where attachments are disassembled

Question 24

What are the steps of cell migration?

Answer 24

1. Protrusion, in which the plasma membrane is pushed out at the front of the cells
2. Attachment, in which the actin cytoskeleton connects across the plasma membrane (via focal adhesions) to the substratum
3. Traction, in which the bulk of the trailing cytoplasm is drawn forward

Question 25

Signals that control cell migration: Rho protein family

Answer 25

• Monomeric GTPase (molecular switches that cycle between active GTP-bound state to inactive GDP-bound state)
• Members: Cdc42, Rac and Rho

Question 26

Rho protein family: What is the function of Cdc42?

Answer 26

triggers actin polymerization and bundling to form filopodia

Question 27

Rho protein family: What is the function of RAC?

Answer 27

promotes actin polymerization at the cell periphery, leading to the formation of sheet-like lamellipodial extension

Question 28

Rho protein family: What is the function of Rho?

Answer 28

promotes both the bundle of actin filaments with myosin II filaments into stress fibres and the clustering of integrins and associated proteins to form focal adhesions.

Question 29

Give an example of pathological cell migration

Answer 29

Tumour metastasis

Question 30

What is metastasis?

Answer 30

The spread of a cancer or other disease from one organ or part to another not directly connected with it

Question 31

What is a cell cycle?

Answer 31

A cell reproduces by carrying out an orderly sequence of events in which it duplicates its contents and then divides in two. This cycle of duplication and division, known as the

Question 32

What is a centrosome?

Answer 32

microtubule-organizing centre that sits near the nucleus in an animal cell, during cell cycle, this structure duplicates to form the two poles of the mitotic spindles. The process of centrosome duplication and separation is known as the centrosome cycle.

Question 33

What is a centriole?

Answer 33

Cylindrical array of microtubules usually found in pairs at the centre of a centrosome in animal cells. They can also be found at the base of cilia and flagella, where they are called basal bodies.

Question 34

What is the mitotic spindle?

Answer 34

array of microtubules and associated between the opposite poles of a eukaryotic cell during mitosis and pulls duplicated chromosome sets apart.

Question 35

What is the mitotic spindle responsible for?

Answer 35

In eukaryotic cells, the mitotic spindle is responsible for separating the duplicated chromosomes and allocating one of copy of each chromosome to each daughter cell

Question 36

What is an Aster microtubule?

Answer 36

star-shaped array of microtubules emanating from a centrosome or from a pole of a mitotic spindle

Question 37

What is a Kinetochore microtubule?

Answer 37

protein complex that assembles on the centrosome of a condensed mitotic chromosome; the site to which spindle microtubules attach

Question 38

What are Interpolar microtubules?

Answer 38

Extend from the opposite sides of the spindle and interact in the middle.

Question 39

What factors affect cell migration?

Answer 39

• Adhesion strength and type of substratum are attached to
• External migratory signals and cues
• Mechanical pliability
• Dimensionality
• The organisation of the cellular cytoskeleton

Question 40

Which is thicker, actin or myosin?

Answer 40

Myosin

Question 41

What are the stages in myosin cell contraction?

Answer 41

Attached
released
cocked
forced generating