Lec5 Flashcards
Characteristics of Basement Membrane
- Separates epithelial layer from its connective tissue support
- 50-80nm thick
the 2 components of basement membrane
- Basal Lamina produced by epithelium
2. reticular lamina, prodiced by connective tissue
Basal lamina contains:
laminin, fibronectin, type 4 collogen, heparin sulfate proteoglucans, nidogen (entactin). Components are glyco proteins which are PAS positive
Reticular Lamina Contains:
type 3 collogen (reticular fibers) Components are glyco proteins which are PAS positive
Laminin
- Maj component of basal lamina; it consists of three chains, A, B, gamma
- has binding sites for integrins, type 4 collagen, entactin and proteoglycans (ie heparin sulfate)
- ties everything together in BL
Fibronectin
- a protein made up of of 2 pp chains cross-linked by disulfide bonds
- 2 forms: cellular (produced by fibroblasts) & plasma (secreted into bloodstream by hepatocytes)
- binding sites for heparin (proteoglycan), integrins, collagen, fibrin
4 CAMs, 2 Ca Dep/ 2 Ca Independent
- Cadherins 2. Selectins 3. Integrins 4. Ig Superfam
Classical Cadherins
- major Components in Ca-mediated adherens junctions
- typically cis and trans homophilic dimers
- include: e-cadherins found in epithelial, N-nerve, P-placenta
E-Cadherins
-most common type, form dimers via a
HVA binding face (histidine, valine, alanine) found at tip of extracellular end of cadherin molecule, Ca ions bind to 4 extracellular domains and facilitate cis-homophillic dimers
-loss of e-cads associated w invasive behavior brain tumors
Catenins
-small proteins that link the cytoplasmic end of a cadherin with cytoplasmic actin, serve as maj. interafce between cads that hold adjacent cells together and the actin cytoskeletons of those cells
-3 forms:
B and Gamma-attached to cytoplasmic end of cadherin, beta ttached to alpha
alpha: binds directly to cytoplasmic actin
Selectins
binds to carbohydrates so part of lectin group
-4 carb binding iste located at carb-recog. domain (CRD) at extracellular end of selectin
-Ca binding sites also found near CRD and Ca is reqd for binding activity
-involved in extravasation and homing (17)
p-platelets, e-endothelial, L-leukocytes
Integrins
Glycoproteins mainly involved in cell-extracellular matrix interactions
- consist of 2 subunits: 1 alpha (s-s) (17 kinds) and 1 beta (8 kinds)
- extra cellular domains bind to molecules in extracellular matrix such as fibronectin and laminin
- in hemidesmosomes integrins link basal domains of cells to ECM via intracellular tonofilamnets
Ig Superfam
-possess an extracellular segment w 1 or more folded domains characteristic of immunoglobulins
-members: N-CAM = cell adhesion molecules are neural adhesion molecules that mediate both homo and hertrophilic interactions
I-CAM1 & I-CAM2- 1 facilitates transendothelial migration of leukocytes
Adherins
A category of junctional complexes, anchor cells together and reinforce the physical integrity of tissues and cells that make up th tissues
-found on basolateralsurfaces of epithelial cells
Occludens
A category of junctional complexes, establish an impermeable barrier btwn adjacent cells, esp. epithelial, preventing paracellular transport & maintains conc. differnces btwn environemnts on either side of epithelial sheets
Gap Juntions 1
A category of junctional complexes, composed of molecular pores that enable cells to rapidly exchange ions and small molecules tht help coordinate activities among the cells that make up the tissue
Zonula
A type of junction that can be either adherens or occludens, zonula complexes travel all the way around the cell & link all neighboring cells to central cell. “belt like complexes”
-associated w intracellular actin
Macula
a “spot” or snap-like junction. Adherens variety and often referred to as desmosomes (lateral domain) or hemidesosome (basal domain), associated w intracellular intermediate filaments (tonofilaments)
Hemidesmosome
anchroing junctions that anchor the basal domain of the epithelial cell to basal lamina
Hemidesmosome consists of:
cytoplasmic plate associated w int. filamnets such as keratin, a membrane plaque linking the hemidesmosome to the basal lamina via anchrng filaments (laminin 5) and integrin
-at 1 time hemidesmosome were thoght to be half a desmosome
Zonula Occludens
-“tight junctions”, belt like occluding junction, barrier against paracellular transport
JAMs and Nectin
members if Ig Superfam, stabalized by s-s bonds, form cis homodimers that facilitate cell adhesion
-nectin is associated w intracelular molecule afadin, JAMs w afadin & ZO-1
Focal Adhesions
spots that anchor the cell to the ECM via integrins, may be very stable or high turnover, ECM portion of the integrins may be folded close to the plasma membrane and unattached to ecm, cystolic signals may cause the integrin heads to unfold and attach to ECM components such as fibronectin or laminin