1. Cytoplasmic membranes-1 Unit objective: To understand that materials in cell are shuttled from one part to another via an extensive membrane network

2. Cytoplasmic membranes-1 Lecture outline: overview of endomembranes how materials move from compartment to compartment specialized functions of the endoplasmic reticulum

3. regulated secretory pathway constitutive secretory pathway lysosome late endosome nucleus Golgi complex cis trans medial cisterna Cytoplasmic membranes-1 secretory vesicle secretory granule rough endoplasmic reticulum exocytosis

4. nucleus Golgi complex cis trans medial cisterna Cytoplasmic membranes-1 endocytic pathway rough endoplasmic reticulum

5. Cytoplasmic membranes-1 movement of molecules (proteins, lipids, neurotransmitters) from donor to acceptor compartment - VESICULAR TRANSPORT

6. nucleus Golgi complex cis trans medial cisterna rough ER secretory proteins membrane proteins Routing signals in primary amino acid sequence resident ER proteins plasma membrane proteins lysosomal proteins nuclear proteins

7. nucleus Functions of the endoplasmic reticulum smooth rough

8. Smooth Endoplasmic Reticulum smooth ER of Leydig cell of testis (site of steroid hormone synthesis) Functions: synthesis of steroid hormones (endocrine cells of gonad and adrenal cortex) detoxification of organic molecules (ethanol, barbiturates) glucose release from liver Ca 2+ sequestration

9. Rough Endoplasmic Reticulum Synthesis of: proteins carbohydrate chains phospholipids PROTEIN MODIFICATION starting point of BIOSYNTHETIC PATHWAY Functions:

10. Rough Endoplasmic Reticulum Protein synthesis on ribosomes attached to ER membrane: secreted proteins integral membrane proteins soluble proteins destined for life in a membrane bound compartment

11. Rough Endoplasmic Reticulum How does cell “know” which ribosomes to target to the ER membrane? SIGNAL HYPOTHESIS (Nobel Prize for Medicine - 1999) Nascent polypeptides possess N-terminal “address code” targets ribosome complex to ER membrane

12. Synthesis of SECRETED PROTEIN on ER membrane-bound ribosome

13. Synthesis of INTEGRAL MEMBRANE PROTEIN on ER- bound ribosome

14. Rough Endoplasmic Reticulum Phospholipid synthesis in the rough ER

15. Rough Endoplasmic Reticulum 1.head groups are modified enzymatically 2.vesicle has distinct phopholipid composition than ER membrane 3.phospholipids removed from one membrane and inserted into another by phospholipid transferases) Phospholipid synthesis in the rough ER

16. Rough Endoplasmic Reticulum Carbohydrate synthesis in the rough ER glucose NAG mannose dolichol phosphate P

17. Vocabulary endomembranes biosynthetic/secretory pathway exocytosis secretory vesicles lysosome endosome Golgi complex cis, trans, medial cisterna rough endoplasmic reticulum smooth endoplasmic reticulum endocytic pathway address codes for trafficking ribosome signal hypothesis signal peptide (sequence) signal peptidase signal recognition particle (SRP) translocon stop transfer sequence phospholipid transferase dolichol phosphate NASCENT

18. Cytoplasmic membranes - 1 Unit Learning Goals: Overview of endomembranes: a.compare, by illustration, the general function of the endomembrane system within the two basic pathways (biosynthetic/secretory and endocytic) b.illustrate the general process by which molecules (proteins, lipids, neurotransmitters) are moved from a donor compartment to an acceptor compartment c.describe the general mechanism by which specific cell “cargo” (secreted proteins, lysosomal proteins, membrane proteins, nuclear proteins, ER proteins) are routed to their proper destination in the cell via the endomembrane system

19. Cytoplasmic membranes - 1 specialized functions of the ER: a.draw and label an animal cell with nucleus, endoplasmic reticulum, and Golgi apparatus and be sure to illustrate the relationship between the nuclear and ER membrane b.compare the functions of the smooth and rough ER c.compare the types of proteins synthesized on free ribosomes vs. ribosomes on the surface of the rough ER, and describe the molecular determinant on a nascent protein that determines whether its associated ribosome will be targeted to the rough ER membrane d.compare, for an mRNA encoding a secreted or integral membrane protein, the steps that occur between mRNA binding to the ribosome and exit of the synthesized protein from the rough ER

20. Cytoplasmic membranes - 1 specialized functions of the ER, contd: e.illustrate the two basic steps involved in the addition of carbohydrate chains to proteins in the rough ER f.describe in general terms how and where membrane phospholipids are synthesized and how they travel to their final destinations in the cell