Week 9 (Cell Migration and division) Flashcards
(41 cards)
What is Cell migration?
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.
What is metastasis?
During pathological conditions, uncontrolled highly migratory cells are the main cause of tumour invasion and metastasis (tumour cells migrating and growing in distant sites).
Cells can migrate individually or
in a sheet
What are the three major components of the cytoskeleton?
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)
What are the Components of a cytoskeleton?
- Microtubules
- Intermediate filaments
- Actin filaments
What is myosin?
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.
Most myosin molecules are composed of
- 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
Actin-Myosin interaction in cell contraction: Attached
- 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
Actin-Myosin interaction in cell contraction: Released
- 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.
Actin-Myosin interaction in cell contraction: Cocked
- 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.
Actin-Myosin interaction in cell contraction: Force-generating
- 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’.
What are the Important structures involved in cell migration?
- Filopodia
- Lamellipodium
- Focal Adhesions
- Cortex
- Transverse Arcs
Describe the properties of filopodia
Thin, spike-like protrusion with an actin filament core, essentially one-dimensional
Describe the properties of lamellipodium
Two-dimensional sheet-like structures, containing a cross-linked mesh of actin filaments
What is the function of Focal adhesions?
Name one of the major components of focal adhesions
- 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.
What is Focal adhesion kinase (FAK)?
A focal adhesion-associated protein kinase involved in cellular adhesion, spreading and migration.
What does FAK bind to?
What does this initiate?
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.
Actin Arrays: Ventral stress fibres
Associate with focal adhesions at both ends, located on the ventral surface of the cell, and function in adhesion and contraction
Actin Arrays: Transverse arcs
Not directly linked to focal adhesions, and typically flow from the leading edge of the cell, back towards the cell centre
Actin Arrays: Dorsal stress fibres
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
What does cell migration require?
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.
What does the leading edge of a migrating cell contain?
The leading edge of a migrating cell is broader and contains lamellipodia and/or filopodia
What happens at the trailing edge?
The trailing edge is called the trail and is where attachments are disassembled
What are the steps of cell migration?
- Protrusion, in which the plasma membrane is pushed out at the front of the cells
- Attachment, in which the actin cytoskeleton connects across the plasma membrane (via focal adhesions) to the substratum
- Traction, in which the bulk of the trailing cytoplasm is drawn forward
