The secretory pathway

3-D model of the Golgi region.

Fig. 2. 3-D model of the Golgi region. By using the software imod, each modeled object could be extracted and viewed in any given orientation and in context with any other object(s) to analyze complex morphologies with minimal ambiguity. (A) The seven cisternae that comprise the Golgi in the region modeled. C1, light blue; C2, pink; C3, cherry red; C4, green; C5, dark blue; C6, gold; C7, bright red. (B) The ER (yellow) traverses the Golgi stack at multiple points and extends in opposite directions beyond the cis-most and trans-most cisternae. (C) The Golgi displayed in the context of all organelles, vesicles, ribosomes, and MTs visible by EM in the modeled region. ER, yellow; membrane-bound ribosomes, blue; free ribosomes, orange; MTs, bright green; dense core vesicles, bright blue; clathrin-negative vesicles, white; clathrin-positive compartments and vesicles, bright red; clathrin-negative compartments and vesicles, purple; mitochondria, dark green. Bars = 500 nm. Marsh B. J. et al. Proc Natl Acad Sci U S A. 2001 98(5): 2399–2406.

Different trafficking pathways have different coat-proteins and GTP-binding proteins

Clathrin

Clathrin Adaptors

Formation of clathrin-coated vesicles

Dynamin mediates pinching off of clathrin/AP-coated vesicles

Trafficking of soluble lysosomal enzyme from the trans-Golgi to lysosomes through mannose 6-phosphate receptor

Our daughter Taylor was born with a rare disease called I-cell. She was trached when she was three years old. She is nine years old now. She is ventilator dependent. Taylor is a very happy child and the ventilator does not seem to bother her in her daily activity.September 22, 2005: Sadly Taylor passed away this evening

Lysosomal storage Diseases

I-cell disease - multiple enzymes are missing from the lysosomes.

Genetic defect – lack the N-acetylglucosamine phosphotransferase

Secretory vesicles budded from trans-Golgi network

Proteolytic processing of proproteins in the

constitutive and regulated secretion

pathways

Protein sorting from trans-Golgi network in polarized epithelial cells

Wenxia:

1. Proteins for different surfaces are sorted into different vesicles that are associated or contain distinct Rab and v-SNARE.

2. Lipid raft for apical sorting and YXXΦ for basolateral sorting.

3. Transcytosis for apical sorting.

Wenxia:

1. Proteins for different surfaces are sorted into different vesicles that are associated or contain distinct Rab and v-SNARE.

2. Lipid raft for apical sorting and YXXΦ for basolateral sorting.

3. Transcytosis for apical sorting.

Endocytosis - Pathways

Clathrin-mediated

Caveolin-mediated

Actin-mediated

pinocytosis

receptor-mediated

macropinocytosis

phagocytosis

Endocytosis - Functions

Uptake nutrients

Maintain cell membrane homeostasis

Regulate signaling

Pathogen entry and protection

Cell type-specific functions

Endocytic pathway

TGN pH 6

pH 4.5Rab7Rab9

Rab5

Rab4

Endocytic pathway under electron microscope

Multivesicular body and lysosomes

Fig. 1. The role of ubiquitylation in protein sorting to multivesicular bodies.

Common mechanism for formation of multivesicular endosomes and budding of HIV from plasma membrane

Transcytosis of maternal IgG across the intestinal epithelial cells of new born mice

Synapse

Release of neurotransmitters and the recycling of synaptic vesicles