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