Intracellular Compartments and Vesicular Trafficking

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Presentation transcript:

Intracellular Compartments and Vesicular Trafficking August 29, 2018 Tom Gallagher tgallag@luc.edu CTRE Room 234 Extension 64850

Four Introductory Slides

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

Vesicle trafficking is continuous, specific, often two-way

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

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)

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

Distinct coat proteins are used for secretory and endocytic pathways

COP II vesicles at the transitional ER (anterograde transport)

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

COPI vesicles at the Golgi (retrograde transport)

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

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

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

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

The coat proteins drive most of the vesicle morphogenesis

Dynamin assists with the membrane fission process Alberts, Fifth Ed., Fig. 13-12

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

The Golgi apparatus is a vesicle transport hub

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

Formation of secretory storage granules

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

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

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

Phosphotidyl inositols “mark” membrane domains

Rabs and Rab effectors also “mark” membrane domains

Vesicles have diverse “markings” on them

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

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

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

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

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

The steps in vesicular transport Front. Endocrinol., 17 January 2011 | doi: 10.3389/fendo.2011.00001 Rab proteins and the secretory pathway: the case of Rab18 in neuroendocrine cells Rafael Vázquez-Martínez1,2 and Maria M. Malagón1,2*