1. Intracellular Compartments and Vesicular Trafficking
August 29, 2018
Tom Gallagher
CTRE Room 234
Extension 64850

2. Four Introductory Slides

3. Proteins made in the ER are transported in vesicles comprising the exocytic pathway
Proteins from the cell exterior are transported in vesicles comprising the endocytic pathway

4. Vesicle trafficking is continuous, specific, often two-way

5. Vesicular transport involves:
Cargo selection / loading
(2) Vesicle budding
(3) Vesicle transport
(4) Vesicle targeting
(5) Vesicle fusion / cargo delivery

6. Same steps in exocytosis and endocytosis
(4) Targeting
(5) Fusion
exo
endo
(1) Cargo selection
(3) Transport
(2) Budding
Figure 13-66a Molecular Biology of the Cell (© Garland Science 2008)

7. Vesicular transport involves:
Cargo selection / loading
(2) Vesicle budding
(3) Vesicle transport
(4) Vesicle targeting
(5) Vesicle fusion / cargo delivery

8. Distinct coat proteins are used for secretory and endocytic pathways

9. COP II vesicles at the transitional ER (anterograde transport)

10. GTP-binding proteins regulate coat and vesicle assembly
Sar1-GAP

11. COPI vesicles at the Golgi (retrograde transport)

12. Clathrin vesicles at the trans-Golgi and plasma membranes (endocytosis)

13. Low Density Lipoprotein (LDL) endocytosis: Clinically important cholesterol regulation

14. Defective LDL receptors that can not associate in clathrin-coated pits will cause hyper-cholesterolemia

15. Vesicular transport involves:
Cargo selection / loading
(2) Vesicle budding
(3) Vesicle transport
(4) Vesicle targeting
(5) Vesicle fusion / cargo delivery

16. The coat proteins drive most of the vesicle morphogenesis

17. Dynamin assists with the membrane fission process
Alberts, Fifth Ed., Fig

18. Vesicular transport involves:
Cargo selection / loading
(2) Vesicle budding
(3) Vesicle transport
(4) Vesicle targeting
(5) Vesicle fusion / cargo delivery

19. The Golgi apparatus is a vesicle transport hub

20. A central role of the Golgi is to sort and process membrane proteins and secreted proteins

21. Formation of secretory storage granules

22. Protein secretion occurs by both a regulated and non-regulated (constitutive) pathway

23. Vesicular transport involves:
Cargo selection / loading
(2) Vesicle budding
(3) Vesicle transport
(4) Vesicle targeting
(5) Vesicle fusion / cargo delivery

24. COPI, COPII and clathrin are removed after vesicle budding: Other factors then control vesicle targeting ?

25. Phosphotidyl inositols “mark” membrane domains

26. Rabs and Rab effectors also “mark” membrane domains

27. Vesicles have diverse “markings” on them

28. Rabs and Rab effectors direct transport vesicle movement along the cytoskeleton
GTP
transport vesicle
Actin or Microtubule filaments
motor protein
Rab effector

29. Rabs and Rab effectors mediate docking and fusion of transport vesicles with their correct target membrane

30. SNARE proteins contribute to specificity in vesicle targeting and promote vesicle fusion to its target

31. The SNAREs have to be taken apart to be re-used for another round of membrane fusion

32. Botulism toxin poisons neurons by cleaving SNAREs; toxin is now re-purposed as “BOTOX”

35. The steps in vesicular transport
Front. Endocrinol., 17 January 2011 | doi: /fendo
Rab proteins and the secretory pathway: the case of Rab18 in neuroendocrine cells
Rafael Vázquez-Martínez1,2 and Maria M. Malagón1,2*