- tight junctions

- seal epithelial cells at apical layer

- separate apical proteins from basal layer

- composed of integral proteins (claudins and occludins) that form strands (more strands = more strength)

- Ca²⁺ dependent

- mediate cell-cell and cell-ECM attachment

- Four types:

1. adherens
2. desmosome
3. hemidesmosome
4. focal adhesions

Anchoring junction at apical layer that uses actin-mediated cell-cell attachment

- composed of cadherins (Ca²⁺ dependent glycoproteins)

- bind intracellular proteins (catenins, vinculin, α-actinin)

- can coordinate morphological tissue changes, e.g. forming a vessel

Anchoring junction at the basolateral surface that mediates cell-cell attachement through intermediate filaments.

- gives mechanical strength

- composed of Ca2+ dependent cadherins (desmogleins, desmocollins)

- bind intracellular attachment proteins (desmoplakin, plakoglobin)

Anchoring junction that mediates cell-ECM attachment via intermediate filaments at the basal layer.

- binds extracellular laminin

- uses intracellular attachment protein, plectin

Anchoring junction that mediates cell-ECM attachment via actin "stress fibers".

- important in movement

- bind extracellular fibronectin and laminin

- use intracellular attachment proteins (vinculin, talin, α-actinin)

- Mediate cell-cell communication

- located at basolateral surface, below adherens

- form connexon channel that allows small molecular transport

• 6 connexins per connexon
• aggregate in response to 2nd messenger stimuli
• 14 different in the body

Three main domains:

1. ECM-domain that binds ECM or another CAM
2. transmembrane domain
3. cytosolic domain that binds adapter proteins

Types include cadherins, selectins, and integrins

• E-cadherin: epithelial
• P-cadherin: placental or epidermal
• N-cadherin: nervous or muscle

All are:

- Ca²⁺ dependent

- important in embryonic cell-adhesion

- exhibit homophilic binding.

Transmembrane, Ca²⁺ dependent cell-cell adhesion molecule

• bind carbohydrates (lectins), i.e. heterophilic
• found mostly in blood vessels
• Three types:

1. L-selectin: leukocytes (WBCs)
2. P-selectin: platelets
3. E-selectin: endothelial

Neural cell adhesion molecule:

• NOT dependent on Ca2+
• homophilic
• 20 different types
• specificity

Composed of:

• glycosaminoglycans (GAGs)
• fibrous proteins (collagen, elastin, laminin, fibronectin)

Functions to:

• Anchor cells
• Mediate wound healing
• Aid embryonic development

The ECM is created (fibroblasts) and mediated by the cells within it

ECM component that is:

• unbranched polysaccharide chain
• forms gel (attracts Na⁺ and water) 
• resists compression
• synthesized in three steps:

1. core protein in secretory pathway
2. polysacch. addition in ER via glycosyl transferase
3. saccharide elongation in Golgi

• Two main types:

1. Proteoglycan
2. Hyaluron

Type of GAG that is:

• (-) charged
• forms gels and separates cells
• crucial in heart development
• crucial in wound healing

Type of GAG that is composed of:

• highly variable core protein (aggrecan, syndecan)
• multiple GAGs

Function:

• Sequester growth factors
• present hormones to cell receptors
• fill space and provide support

Types of collagen

Type I: most abundant; skin and bone

Type II: cartilage

Type III: skin, blood vessels, organs

Type IV: forms basil network, gives tensile strength

Type IX & XII: promote further aggregation into fibers

Collagen assembly

1. Synthesis and glycosylation of procollagen in rough ER, formation of triple helix
2. Further glycosylation and vesicle budding from Golgi
3. Exocytosis
4. Cleavage into collagen and self-assembly into fibrils in ECM
5. Collagen fiber formation mediated by IX and VII in ECM

ECM component that is:

1. most prominent in skin, lungs, blood vessels
2. composed of fibrillin and elastin
3. synthesized only by fetal and juvenile fibroblasts
4. excellent recoil and stretch

Component of ECM that:

1. binds other ECM components
2. two types: fibronectin and laminin

Adhesive glycoprotein that:

1. forms heterodimers
2. plasma form associated with clotting & wound healing
3. tissue forms fibrils
4. R - G - D sequence mediates binding

Adhesive glycoprotein that:

1. tends to form sheets
2. binds epithelial cells to basement membrane

i.e. "laminins present on the lamina"

   3. associated with muscular and PNS regeneration

"Basement membrane"

Extracellular component that:

1. underlie all epithelia and some other tissues
2. thin sheet of proteins and carbohydrates
3. provides basis for tissue repair, polarity, differentiation
4. structure is tissue dependent:

• epithelial basil lamina regulates transport
• muscular basil lamina provides surrounding support
• kidney basil lamina separates blood and urine
  • damage to lamina can lead to excretion of good proteins in the urine (Diabetes)
    

ECM degradation peptide that:

1. use calcium or zinc
2. degrade ECM for differentiaion, proliferation, remodeling, and tissue repair
3. usually up-regulated by metastatic cancer cells

ECM degradation peptide that:

1. regulated by serpins (serine protease inhibitor)
2. regulated by cell-surface receptors

Cell-surface, integral membrane receptor associated with ECM binding:

1. Beta1 - bind to ECM
2. Beta2 - bind to other cells (only in lymphocytes)

Cytoskeletal component:

1. gives strength and shape
2. cell movement
3. composed of actin filaments
   • polarity => grows from (+) end
4. Muscle contraction
   • myosin motor protein

Cytoskeletal component:

1. provide strength
2. NOT polarized
3. do NOT require ATP/GTP hydrolysis

Cytoskeletal component:

1. polymer of α & β dimers
2. nucleate at centrosome (center of cell)
3. polarized => grow at (+) end
4. cilia & flagella use 9:2 arrangement
   • movement uses ATP
   • motor proteins, dyenin (-) and kinesin (+)
5. can rapidly disassemble and reassemble
   • important for cell division
   • disrupted by taxol and cholchicine

Step-by-step extension of cell membrane for movement in tissue repair:

1. Extension - using lamellipodium
2. Adhesion - forms focal adhesion from stress fibers
3. Translocation - cell body actually moves
4. De-adhesion - breaks adhesions via stress fiber contraction

Actin and myosin polymerizing "stress fibers" drive movement

Invasive actin-based cellular protrusion:

1. found on metastatic cancer cells
2. contain adhesion proteins and matrix-degrading enzymes

Motor protein associated with microtubules. Functions in cargo transport by utilizing ATP. Forms of kinesin vary and are cargo-specific.

Travels from (-) to (+) end.

Thus, travels from centrosome to cell membrane.

Motor protein associated with microtubules. Associated with ATP-hydrolyzed cell movement. 

Moves from (+) to (-) end.

Thus, moves from PM to centrosome.