Last Class

1. ECM components: glycosaminoglycans (GAGs) and fibrous proteinsa. GAGs: Hyaluronan; Chondroitin sulfate and dermatan sulfate; Heparan sulfate; Keratan sulfateb. Fibrous proteins: collagen, elastin, fibronectin, laminin

2. basal laminae, neuromuscular junction

3. Cell-ECM interaction, ECM degration

4. ECM receptor, integrins

• Cell Junctions, Cell-Cell Adhesions

CrossSection View of Intestine Wall

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Tight Junctions

Claudins, Occludins

ZO Proteins

Tight Junctions as barriers to solute diffusion

Electron-dense tracer is added in the apical (B) and basal sides of the cells (C).

Tight Junctions Structures

Freeze-fracture EM

Models for Tight Junctions

Claudin and occludin

Anchoring Junctions

Connecting cytoskeletons

Two Classes of anchoring junctions

Anchoring junctions

1. Adherens junctions (cell-cell)2. Desmosomes (cell-cell)3. Focal adhesions and hemidesmosomes

(cell-ECM)

Adherens Junctions

Adherens Junctions

Folding of an epithelial sheet to form an epithelial tube

Desmosomes

Desmosomes

Focal Adhesion

hemiDesmosomes and desmosomes

Gap Junctions

Size of molecules allowed to pass

Gap Junctions

Gap Junctions in EM

Regulation of Gap Junctions

Rabbit retina and dopamine treatment

Switch between rod and cone photoreceptors

Lucifer yellow injection

Gap Junctions Functions

1. Rapid communication between neighboring cells, e.g. cardiomyocytes need synchronized actions

2. Communication beyond nerve system, e.g. hepatocytes beyond sympathetic nerves need to be informed to produce glucose from glycogen

3. Embryogenesis, form specific tissue with coupled group of cells

Summary of cell junctions

Summary of cell junctions

Cell-Cell Adhesions

Cell to Tissue mechanism

A Simple Model

Cell to Tissue mechanism

A More Complex Model

Cell adhesion molecules (CAM)

Cell-cell Adhesion

cadherins

Cell-cell Adhesion

Regulation of cadherins

The distribution of E-cadherin (ectoderm) and N-cadherin (neural tube) in Chick embryo

Three mechanisms of cell-cell adhesions

Cadherin-dependent Cell Sorting

Cadherins are linked to actin filaments

Adherens Junction Formation

movie

Selectin-mediated cell-cell adhesion (blood cell rolling)

E-selectin, L-selectin, P-selectin

White Blood Cell Rolling and Adhesion

Movie

Neural cell adhesion molecule (N-CAM),

intercellular adhesion molecule (ICAM)

Calcium-independent

Immunoglobulin (Ig) superfamily

Summary Diagramnon-junctional adhesion proceeds junctional adhesion

Summary

1. Junctions: Occluding Junctions, Anchoring Junctions, Communicating Junctions2. Occluding Junctions: Tight Junction3. Anchoring Junctions: adherens Junction4. Communicating Junctions: Gap Junction 5. Cell-Cell Junction: adherens junction, cadherins

Overview of the Cell • Membrane structure and components, membrane proteins, carrier

proteins, channel proteins• Signaling transduction, ligand-receptor interactions, ion-channels,

GPCRs, RTKs, molecular switches (kinase, GTPases), molecular complex formation and signaling integration, signaling desensitization,

• GPCR, GPCR signaling: cAMP, Calcium (CaM Kinase as memory molecule)

• RTK, RTK signaling: Ras, PI3K (PLC, Akt, Rac) • Protease mediated signaling: NF-kB • Cytoskeleton: microtubules, actin, intermediate filament• Regulation of microtubules and actin• Molecular motors: myosin (Sliding Acto-Myosin filaments), kinesin• Cell migration and its relationship with actin filaments• Extracellular matrix: GAG, fibrous proteins (collagen, elastin,

fibronectin, laminin)• Basal laminae, cell-ECM interaction, integrins, cell-cell adhesion (tight

junction, adherens junction, gap junction), cadherins