Chapter 13: Vesicular Traffic

Transcription

1 Chapter 13: Vesicular Traffic Know the terminology: ER, Golgi, vesicle, clathrin, COP-I, COP-II, BiP, glycosylation, KDEL, microtubule, SNAREs, dynamin, mannose-6-phosphate, M6P receptor, endocytosis, pinocytosis, phagocytosis, endosome, autophagy,

2 Vesicular Traffic The ER is the starting point for proteins destined for several final locations. Resident proteins of ER, Golgi, lysosome, plasma membrane It is also the starting point for proteins destined for secretion: -Hormones, extracellular matrix proteins

3 Chapter 13: Vesicular Traffic

4 Chapter 13: Vesicular Traffic

5 Vesicular Traffic Movements of these proteins between compartments is mediated by vesicles

6 Vesicular Proteins Most vesicles are coated with proteins such as clathrin and COP

7 Vesicular Proteins These proteins facilitate formation of the vesicle

8 Vesicular Proteins Other proteins (e.g. GTPases) help pinch regions of lipid bilayer to form vesicles

9 SNAREs on the vesicle (v-snare) and on the target membrane (t-snare) help vesicles dock and fuse to membranes Vesicular Fusion

10 Vesicular Fusion

11 Vesicular Fusion

12 ER Golgi The ER is the site of co-translational import, the gateway for entry proteins destined for many other compartments, and secretion -The next stop in their travels is the Golgi

13 ER Golgi While in the Golgi, many (proteins and lipids) are modified by glycosylation (addition of complex carbohydrate chains at specific amino acid residue)

14 ER Golgi Each compartment of the Golgi (e.g., cis, medial, trans) has characteristic modifying enzymes

15 ER Golgi Vesicles formed in the ER move membrane proteins and soluble proteins to the Golgi complex (1) How are vesicles formed? (2) How are these vesicles targetted to the Golgi? (3) How do cells avoid sending the wrong proteins (i.e., how do they retain ER proteins in the ER?)

16 ER Golgi (1) How are vesicles formed? One type of protein (COP II) binds to the ER membrane and extracts a layer of membrane to form a vesicle

17 ER Golgi (2) How are these vesicles sent to the Golgi? (Fig 13-20) -These vesicles cluster into a network then get transported on microtubules to the Golgi

18 ER Golgi (3) How do cells avoid sending the wrong proteins (i.e., how do they retain ER proteins in the ER?) -As soon as the network is formed, COP-I vesicles form to return ER proteins to the ER

19 ER Golgi Resident ER proteins (e.g. BiP) have characteristic signal sequences (e.g., KDEL) that bind and activate a receptor (these recruit COP-I proteins to form a vesicle, which is sent back to the ER

20 Golgi endosome lysosome Lysosomes are degradative organelles that process substances from: -outside the cell (via endocytosis of solutions, or phagocytosis of particles) -inside the cells (i.e., damaged organelles are degraded by autophagy)

21 Golgi endosome lysosome

22 Golgi endosome lysosome How do lysosomal proteins get targeted to the lysosomes? Lysosomal proteins (e.g.hydrolase) have a unique glycosylation pattern with a terminal mannose residue As it transits the Golgi, a the mannose is phosphorylated to form mannose-6-phosphate

23 Golgi endosome lysosome A M-6-P receptor in the Golgi binds the protein and undergoes a conformational change, leading to formation of a clathrin-coated pit

24 Golgi endosome lysosome

25 Golgi endosome lysosome Vesicle is carried to the lysosome, where it fuses -once ph drops, the enzyme is released

26 Endocytosis Phagocytosis ( cell eating ) and pinocytosis ( cell drinking ) involve formation of vesicles of cell membrane, capturing extracellular particles

27 Endocytosis Phagocytosis is triggered when a membrane receptor binds a specific ligand (e.g. Fc domain of an antibody) (Fig 13-39)

28 Endocytosis Clathrin coated vesicles mediate pinocytosis (Fig 13-41)

29 Exocytosis Cells use 2 pathways for secretion: constitutive and regulated

30 Exocytosis Proteins are often proteolytically processed during transit through the Golgi/endosomes

31 Exocytosis Regulated secretion is required for hormones. Storage vesicles are triggered to dock and fuse to cell membranes (e.g. Fig 13-57)

32 Exocytosis Secretion is triggered in response to signaling pathways (e.g. Fig 13-59)