Lecture 2 Flashcards
Basal Lamina Components
- Laminin
- Type IV collagen
- Entactin (nidogen) attached to laminin and collagen
- Proteoglycans
Basement Membrane 2 components
- basal lamina, produced by epithelium
- reticular lamina, connective tissue
Laminin
- Major component of BL
- 3 chains: alpha, beta, gamma
- binding sites for integrins, type IV, entactin, and proteoglycans
Type IV collagen
- doesn’t form fibrils like type I
- prodcued by epithelial cell, unlike type I which is secreted by fibroblast
Fibronectin
- protein made up of two polypeptide chains cross-linked by disulfide bonds
- Cellular, produced by fibroblasts, part of extracellular matrix
- Plasma, secreted into bloodstream by hepatocytes
Fibronectin binding sites
- can bind to themselves and others, forming EM support chain
- Heparin (proteoglycan)
- Integrins
- Collagen
- Fibrin
Calcium Dependent CAMs
- cadherins
- selectins
Calcium Independent CAMs
- integrins
- Immunoglobulin superfamily molecules
Classical Cadherins
- major components in Ca mediated adherens junctions
- cis/trans homophilic dimers
- E-N-P-cadherins
Nonclassical Cadherins
- desmocollins and desmogleins
- found in desmosomes (macula adherens)
Homophilic Dimers
- two similar molecules that bind together
- cis, two identical bin from same cell
- trans, two identical from different cells bind
E-cadherins
- found in epithelial tissue, most common
- adhere to one another
- HVA binding face
- loss associated with invasive behavior of tumors
N-cadherins
-found in nerve cells
P-cadherins
-found in the placenta
HVA binding face
- histidine-valine-alanine sequence
- found at tip of extracellular end of cadherin
- facilitates formation of trans-homophilic (lets one bind to another)
- Ca binds to four extracellular domains to facilitate cis
Catenins
- small proteins that link cytoplasmic end of cadherin with actin
- three forms alpha, beta, gamma
- serve as major interface between cadherins that hold adjacent cells together and the actin cyto of those cells
Beta and Gamma catenins
- plakoglobin catenins
- attach to cytoplasmic end of a cadherin
- beta also serve as transcription cofactor
- beta attached to alpha catenin
Alpha Catenin
-binds directly to cytoplasmic actin
Selectins
- bind to carbs, belong to lectin
- bind on carbohydrate-recognition domain (CRD)
- Ca required to bind on CRD
- involved in movement of leukocytes (blood cells) to tissues (extravasation)
Classes of Selectins
- P-selectins: platelets
- E-selectins: activated endothelial cells
- L-selectins: leukocytes
Integrins
- glycoproteins involved in cell-extracellular matrix interactions
- bind to both EM and cytoplasm
- two subunits, one alpha (17 kinds) one beta (8 kinds)
- extracellular domains bind to fibronectin, laminin
- interact with RGD (arg-gly-asp)
Connecting Proteins
-talin, vinculin, alpha-actinin
Tonofilaments
- in hemidesmosomes, integrins link basal domains via intracellural tono
- resist tension
Immunogobulin Superfamily
- possess an extracellular segment with 1 or more folded domains
- N-CAM: neural adhesion molecules, mediate homo and heterophilic interactions
- I-CAM-1, I-CAM-2: facilitate transendothelial mmigration of leukcytes
Adherens
- Junctional complex, anchor cells together and reinforce integrity
- found on basolateral surfaces of epithelial cells
Occludens
- junctional complex, establish an impermeable barrier etween cells
- prevent paracellular transport
Gap Junctions
- composed of molecular pores, enable cells to rapidly exchange ions
- can shut down if injured
Zonula
- tight junction, can be adherens or occludens
- travel around cell and link neighboring cells
- belt-lie complexes
- associated with intracellular actin
Macula
- spot or snap-like junction
- adherens, desmosomes or hemi
- intracellular intermediates (tonofilaments)
Adherens
- anchoring junctions characterized by intercellular spaces
- spaces filled with cadherin protiens
- desmogleins, desmocollins
- cadherin proteins anchored to cyto plaques containing desmopakin, plakoglobin
Desmogleins
- 1 & 2 found in epidermis
- autoantibodies to 1 result in pemphigus foiaceus
Heidesmosomes
- anchor basal domain of epithelial to basal lamina
- cyto pate w/ intermediate filaments lie keratin
- membrane plaque linking hemi to basa via laminin 5 and integrins
Zonula Occludens
- JAMs and Nectin, both Ig family
- nectin intracellular molecule, afadin
- JAMs intracellularly with both afadin and ZO-1
Focal Adhesions
- spots that anchor the cell to EM via integrins
- intracellular attachment to actin filaments via connecting proteins
Gap Junctions
- communicating junctions
- composed of connexons, each with 6 connexins, forming hexagonal structure with hollow center
- facilitate movement of molecules
- often clustered into patches