How do coated vesicles go to the right place and fuse with the right membrane? The “SNARE” hypothesis.

How do coated vesicles go to the right place and fuse with the

right membrane?

The “SNARE” hypothesis

SNARE

• Vesicle-SNAP-receptors (v-SNAREs)

• Target-SNAP-receptors (t-SNAREs)

• SNAP=soluble NSF attachment proteins

• NSF=N-ethylmaleimide-sensitive factor

Lysosomes

• Digestive enzymes

• Low pH (4-5)

• Develop from late endosomes/hydrolases from Golgi

• Activated by lowering the pH

Extracellular components

• Cell walls

• Extracellular matrix– Bone– Cartilage– Connective tissue

Types of molecules in ECM

• Structural proteins—strength/flexibility– Collagen– Elastin

• Proteoglycans--matrix• Adhesive glycoproteins—stick cells to

matrix– Fibronectins– laminins

Collagen--strength

Synthesis--fibroblasts

Elastin--flexibility

Glycosaminoglycans

Proteoglycans—hydrated matrix

Adhesive glycoproteins

• Extracellular– Fibronectins– Laminins

• Cell surface– Integrins

Fibronectins

• Group of adhesive glycoproteins

• 2 long linked proteins

• Several binding domains

Fibronectin roles

• Anchor cells to ECM

• Maintain cell shape

• Cell movement

• Blood clotting

Laminins• Found in basal laminae

– Special ECM– Under epithelial cells– Separates them from connective tissue

• Role of basal laminae– Support– Permeability barrier

• Contain– Type IV collagen– Proteoglycans– laminins

Laminins

• Very large proteins

• 3 linked peptides

• Multiple domains

What binds the cells to the ECM?

Integrins

• Groups of transmembrane proteins

• Link cytoskeleton to ECM

• Fibronectin receptor is best known

Cell-cell interactions

Cell-cell adhesion

Cell-cell communication

Cell-cell adhesion

• Cell adhesion molecules (CAMs)– Lots of them– Involved in many cellular processes

• Cadherins– Adhesive glycoproteins

Cell juctions

• Adhesive junctions– Strong links

• Tight junctions– Prevent leaks between cells

• Gap junctions– Forms direct link between cells

Adhesive junctions

• Desmosomes• Hemidesmosomes• Adherens junctions• Focal adhesions

All contain- intracellular attachment proteins—link to cytoskeleton- transmembrane linker proteins—link the cells

Desmosomes—rivets between cells

Adherens junctions

• Belt around cell• Connects to actin, not

tonofilaments• Look a lot like

desmosomes• Found in

– Heart– Epithelial layers

• Oftern form belt

• Called “focal adhesion” if connects to ECM

Tight junctions

Gap junctions

• Direct electrical connection

• Formed by connexons– Protein=connexin

• Prominent in muscle and nerve—e.g. electrical tissues

• Form of cell-cell communication

Cell walls

Plant cell walls

• Cellulose (40%)• Branched polysaccharides

– Hemicellulose (20%)– Pectins (30%)

• Extensins--glycoproteins (10%)

• Lignins—woody tissues– Insoluble aromatic alcohols– Cross-link to form wood

Plasmodesmata