Cell cytoskeleton and migration

What are the basic principles of the cytoskeleton function

Provide shape and support to cell

help in formation of vacuoles

holds different cell organelles in place

assists in cell signaling

support intracellular movements like cell organelle migration, transportation of vesicles in/out of cell

What are the components of the cytoskeleton

microfilaments (actin)

intermediate filaments

microtubules (tubulin)

What is the general role of motor proteins

intracellular transport, cell division, and movement

What is the basic principles of cell migration

vital process in development and maintenance of organs

tissue formation during embryonic development, wound healing, and immune responses

What is the largest component of cytoskeleton and where are they found

Microtubules

found in cytoplasm

What proteins make up microtubules

globular protein subunits α-tubulin and β-tubulin

What is the function of microtubules

help cell resist compression, provide track for vesicles, pull replicated chromosomes to opposite ends of dividing cell

What is the structure of cilia and flagella

ring of microtubules wrapped in membrane

What are intermediate filaments (IF)

several strands of fibrous proteins that are wound together

Which component of cytoskeleton is the most diverse group

intermediate filaments

What is intermediate filaments function and number of main classes

structural support, anchor nucleus/ organelles in place

6 main classes

What is keratin and its function

protein in body that helps form the structure of skin, hair, and nails

provide strength and protection

What is type of intermediate filament is acidic keratin and found in hair and nails

IF Type I

larger than IF type II

What is IF type II keratins and where are they expressed

Type II A: expressed in tissues that require high levels of mechanical stress (soles of feet)

Type II B: expressed in tissues subjected to less stress (palms of hands)

What is IF Type III function and examples

tissue integrity (especially muscles, nerves and endothelial cells)

Examples:

• Vimentin

• Desmin

• GFAP (Glial Fibrillary Acidic Protein)

• Peripherin

Where is IF Type III vimentin found

fibroblasts (cells that produce connective tissue) and endothelial cells

Where is Type III IF desmin found

protein that functions in skeletal and cardiac muscle (striated), around Z-discs of sarcomeres

Where is IF Type III Glial Fibrillary Acidic Protein (GFAP) found

astrocytes (cell in nervous system that supports neurons)

Where is Type III IF, Peripherin found

peripheral nerve cells

What are the two types of IF Type IV

Neurofilaments (NF)

α-internexin

What is IF Type IV found and function

neurons of nervous system

supporting axons

What is IF Type V comprised of and its function

Lamins (A, B, & C)

structural proteins found in nucleus forming nuclear lamina

What is IF Type VI examples

Filensin and phakinin

beaded IF that forms lens (like bovine lens

What two forms can microfilament actin be

Free monomer: G-actin

part of polymer microfilament: F-actin (filamentous-actin)

What are the 3 types of motor proteins

1. Kinesins

2. Dyneins

3. Myosins

What is function of Kinesins

transport cargo (organelles, vesicles, or proteins) along microtubules from center of cell to periphery

What is function of motor protein Dyneins

move cargo along microtubules, but opposite direction of kinesins from cell’s periphery toward center

What is the function of motor protein Myosins

Move along actin filaments and involved in muscle contraction, cell movement, and intracellular transport

What is the front end and rear called in migrating cells

“Front” end: leading edge/ lamellipodium

“Rear”: uropodium

What are the 5 steps in cell migration

1. Protrusion of membrane lamellopodia

2. Adhesion to matrix via integrins

3. Contraction of cytoplasm by myosin-based motors

4. Rear release and forward displacement

5. Integrin recycling

How are types of cell migration categorized

based on stimuli, patterns of movement or cellular mechanisms involved

What is Amoeboid Migration and example

rapid flexible migration, cell changes shape via extending/retracting parts of their membrane

Immune cells

What is Mesenchymal Migration and example

slower more adhesive form, cells move through ECM by degrading it (through enzymes like metalloproteinases) and adhering to it

Fibroblasts during wound healing

What is collect migration and example

groups of cells move together in coordinated manner, maintaining cell-cell contacts while migrating as a unit

Epithelial cells moving as a sheet during wound healing

What is Single-cell migration and example

individual cell moves independently in different forms (amoeboid or mesenchymal) dependent on tissue/environment

Cancer cells breaking away from tumor and migrating individually

What is Chemotaxis and example

directed cell migration in response to chemical gradient

Neutrophils moving toward infection sites by following chemoattractants like cytokines

What is haptotaxis (surface) and examples

directed migration in response to gradient of adhesion molecules/ ECM components (immobilized on surface like collagen/fibronectin)

Cells use surface receptors to detect differences in substrate-bound molecules and migrate toward regions with higher concentrations

What is Necrotaxis migration and example

cell migration towards necrotic tissue

macrophages migrating to necrotic tissue to engulf dead cells

What is durotaxis migration and examples

migration directed by stiffness gradients in surrounding tissue/substrate. Cells move toward stiffer areas, common during development and wound healing

What is Electrotaxis (or Galvanotaxis) migration and example

Directed cell movement in response to an electric field

epithelial cells or neurons can sense electric fields and migrate toward/away from source of current

What is Haptokinesis migration and example

non-directional increase in the speed/frequency of migration in response to adhesion molecules (random in direction) and move more actively when in contact with certain ECM components in non-directional manner

Endothelial cells becoming more mobile on certain ECM proteins during formation of new blood vessels (angiogenesis)

What is Autologous Chemotaxis migration and example

cells migrate toward self-secreted signals (autocrine signaling) guiding their own movement

Cancer cells secreting signals to help guide invasive migration

What is Barotaxis migration and example

cell movement in response to pressure gradients, from areas of low pressure to high pressure (or vice versa) 

Endothelial cells may respond to pressure changes in blood vessels

What are some key players in cell migration

RhoA, small GTPase protein and Rho kinase

What inhibitor leads to inhibition of F-actin re-arrangement

RhoA inhibitor, Beraprost

What type of inhibitor abolishes vascular smooth muscle cell (VSMC) migration

Integrin-linked kinase

What does invasion of a cell involve

ECM degradation takes place, involving subcellular structures, invadopodia and podosomes