1 / 47

Endocytosis - Exocytosis

BIOLOGY, Faculty of Pharmacy. 2015. 10. 12. László KŐHIDAI, Med. Habil. MD, PhD., Assoc. Prof. Department of Genetics, Cell- and Immunobiology Semmelweis University. Endocytosis - Exocytosis. Endocytosis. Phagocytosis – solid Pinocytosis – liquid (general) Endocytosis :

lorigale
Download Presentation

Endocytosis - Exocytosis

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. BIOLOGY, Faculty of Pharmacy 2015. 10. 12. László KŐHIDAI, Med. Habil. MD, PhD., Assoc. Prof.Department of Genetics, Cell- andImmunobiologySemmelweis University Endocytosis - Exocytosis

  2. Endocytosis • Phagocytosis – solid • Pinocytosis – liquid (general) Endocytosis: • Uptake of substances • Transport of protein or lipid components of compartments • Metabolic or division signaling • Defense to microorganisms

  3. Predominant cells: unicellular cells macrophages osteoslats throphoblasts Functions: uptake of food partickles immuneresponses elimination of aged cells (RBC) Phagocytosis (1)

  4. Phagocytosis (2) Required: • signal • membrane receptor (Fc receptor for Ab) • formation of pseudopodium • cortical actin network The formed vesicle: phagosome (hetero-; auto-)

  5. Endocytosis • Clathrin-coated vesicles • Non-clathrin coated vesicles • Macropinocytosis • Potocytosis

  6. Clathrin coated pits/vesicles

  7. Function of clathrin coated vesicles • Receptor mediated endocytosis • Selective uptake of molecules • (low environmental conc.) • Membrane receptors • Concentration of ligand (1000x)

  8. Components of coated vesicles

  9. Receptor-mediated endocytosis of LDL

  10. Sorting signals of secreted and membrane proteins to transport vesicles

  11. Selective incorporation of membrane proteins Into the coated vesicles

  12. Endosomal-Lysosomal compartmentStructure • tubular, vesicular • acidic pH - vacuolar H+ ATP-ase - proton pump • early-endosome (EE) and late-endosomes (LE) and lysosomes (L) • EE pH= 6; LE pH=5 • in EE no lysosomal membrane proteins or enzymes (in contrast LE)

  13. Endosomal-Lysosomal compartmentFunction • sorting • transport • degradation • removal of clathrin layer • formation of EE in the EE: • dissociation of receptor-ligand complex - receptor-recycling (e.g. LDL, transferrin) • receptor-ligand complex transported together - receptor down regulation (e.g. EGF)

  14. Pathway of LDL • insulin or other • hormones – • in receptor • mediated • endocytosis

  15. Fate of LDL internalized by receptor-mediated endocytosis

  16. The transferrin-cycle

  17. Late endosome • early endosomes, TGN and autophagosomes feed late endosomes • lysosomal enzymes M-6-P signal is changed, the phosphate group is cleaved - receptors can not bind enzymes • the enzyme content of vacuoles is in the lumen lysosomes

  18. Dissociation of receptor-ligand complex in late endosomes

  19. De Duve, Ch. Nobel-prize - 1974 Lysosomes (TEM)

  20. Lysosomes • enzymes - acidic hydrolases e.g. protease, nuclease, glycosidase, phosphatese • more than 40 types of enzymes • membrane proteins - highly glycosilated protects from the enzymes • transport molecules of the membranes - transports the products of proteolytic cleavage into the cytoplasm • the waste products are released or stored in the cytoplasm (inclusion - residual body)

  21. LAMP = lysosome associated membrane proteins • integrant membrane proteins of • the lysosome • LAMP-2 – tarnsport of cholesterol • LAMP-2 defficiency- autophagy www.helsinki.fi/bioscience/biochemistry/eskelinen

  22. Autophagy - Autophagosome • intake of own components • regulates the number of organells • toxic effects can also induce it

  23. Formation of autophagosome www.helsinki.fi/bioscience/biochemistry/eskelinen E

  24. Non-clathrin coated vesicles • There is no receptor or clathrin in the membrane • The uptake of substances is less selective • Primairly liquide-phase endocytosis

  25. Macropinocytosis • Ruffling of the surface membrane forms inclusions • These „vacuoles” have no membrane • Size 0.2-5 mm - the mass/surface ratio is very good • Significance: • Liquide-phase pinocytosis • Taking probes from the • environment • – antigene recognition • in macrophages Film produced by F. Vilhardt and M. Grandahl.

  26. Caveolae • 50-80 nm, bottle-like infoldings of the surface membrane • endothels, adipocytes • caveolin • potocytosis - caveolae close but not internalized, the materials enter the cytoplasm by a special carrier molecule e.g. vitamine B4 • some other caveolae enter the cell !!!

  27. Caveolae

  28. 33 AA 44 AA C 101 AA N Caveolin oligomers and caveolae assembly

  29. Functions of dynamin Clathrin-mediated endocytosis Membrane retrieval Endosome- to-Golgi transport Secretory vesicle formation in TGF Caveolae Fluid phase endocytosis

  30. Dynamin in the cell

  31. Structure of dynamin Interaction with membranes Interaction with cytosceleton Activation of GTP-ase domain

  32. Dynamin requires GTP hydrolysis to pinching off coated vesicles • The not-hydrolysable GTP-gS is added • Dots represent binding of anti-dynamin antibodies • The long neck shows that however the coated pit was formed, • in the absence of GTP hydrolysis its pinching off is absence

  33. Carrier mediated proteolysis • some molecules can enter lysosome directly from the cytoplasm • the signal of entry: KFERQ (Lys-Phe-Glu-Arg-Gln)

  34. Proteasome • non-lysosomal cleavage of proteins • cylindric, multienzyme complex • parts: ATP binding-, substrate binding-, regulator-domain • location: close to the external part of ER-translocon • ubiquitin - degradation-signal - is required • the non-properly folded or damaged proteins • regulator - eliminator - role e.g. cyclins • cystic fibrosis - Cl- fac. transp. is affected as the responsible membrane protein is broken down in proteosome

  35. Proteasomes

  36. Ubiquitation - proteasome

  37. „Exocytotic” processes

  38. The mannose-6-P pathway and lysosomal enzymes

  39. Exocytosis in TEM

  40. Apical and basolateral targeting in epithelial cell

  41. Transcytosis • the ligands walk around the endosomal compartment • ligands transported from one surface to the other • e.g. immunoglobulins of the colostrum cross the intestinal epithelium by transcytosis

  42. Release of neurotransmitters

More Related