Secretion, Exocytosis & Endocytosis

Lecture 22 BSCI 420,421 Oct 23,24, 2002

An old Cherokee told his grandson about a battle goingon within him. “It is between two wolves, one is evil, full of anger, greed, envy, pride, and ego. The other is good, fullof generosity, kindness, empathy, love, and humility.”“Which wolf wins?” said the grandson.The old Cherokee replied, “The one I feed.”

In addition to lysosomes, two secretory paths diverge from TGN

A. Constiutive pathway

• Continuous

• COP-1 coated ves from TGN

• No stimulus required for exocytosis

• Provides new plasma membrane proteins

• Continuously secreted proteins, e.g.: albumen from liver Igs from plasma cells Collagen from fibroblasts

• Default pathway that requires no additional signal

PM proteins can be targeted to 2 different domains, directly orindirectly

Lipid rafts are often transported to the cell surface as a group.Rich in cholesterol, long chain phospholipids & glycolipids, & Proteins w long TM domains.

B. Regulated secretion

• Specific receptors bind proteins and cluster intoclathrin coated areas of the TGN.

• Proprotein cleaved to mature protein

• Ions pumped out and H20 follows to concentrate

• Stored in secretory granule until stimulus

• Transported by MTs upon stimulus

• Docking, Fusion, & exocytosis, often stim.by Ca2.

• E.g.s: protein hormones, inducers, cytokines, digestive enzymes

Formation ofSecretory Vesicles andMaturation

Maturation involvesloss of clathrin coats, dehydration and concentration,and proteolysis.(pre-proinsulin ->proinsulin ->Insulin)

Gold-labeledAnti-clathrin

Transport (MTs),docking,and fusion.Stimulated by receptor activationthat increasesCa+2 in cells.

Fig 57:

Insulin secretionby exocytosis from pancreaticBeta cell.

In addition to 1) Exocytosis, three other types of secretion:

2) Apocrine secretion

Release of a part of the cytoplasm, surrounded by pl. membrane.Egs: platelets from megakaryocytes, Milk fat globules from mammary gland cells

3) Holocrine secretion

Release of complete cells into & out from a secretory ductEgs: Eccrine sweat gland cells- keep skin moist and oiled.Spermatozoa?

4) Monomolecular secretionProteins secreted one molecule at a time w no membraneEgs: Bacterial secretion, yeast mating pheromones, and otherABC transporter secreted proteins

ENDOCYTOSIS – Uptake of macromolecules into cell in vesicles

1. Phagocytosis 2. Pinocytosis /Receptor-Mediated endocytosis

Ingestion of large particles Activated by receptors on surface e.g. Fc rec for antibodies on WBCs like neutrophils:

Fig 40

Triggers actin & myosin filament assembly &interaction to form pseudopods &engulf particles.

2. Pinocytosis /Receptor-Mediated endocytosis (RME)

A. Formation of clathrin-coated pits

RME was discovered by Brown & Goldstein by looking at skin Fibroblasts of children with Familial Hypercholesterolemia, a genedisease in which excess cholesterol causes early heart attacks.Mutant LDL receptors, so unable to take LDL out of bloodstream.

LDL particle

ApoB protein ~1500 cholesterol

esters

RME of LDL particles

Can also be defective LDL bindingOr defective targeting of receptorto the cell surface

Transcytosis- Eg newborn takes up antibodies from mother’s milk (Colostum) release at neutral pH

Uptake at acid pH

Material from 3 different sources end up in lysosomes

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