Organelles: discrete intracellular units of function with or without a plasma membrane 11/21

1. Organelles: discrete intracellular units of function with or without a plasma membrane11/21 Why are cells are divided into organelles for localized specialization within a cell? What pathways do proteins take post-translation when moving around inside/exiting from the cell? Ribosomes on/off ER make protein from mRNA SER stores Ca++ and modify proteins. How does the Golgi Apparatus participate in exocytosis and endocytosis? How does clathrin help mediate receptor-mediated endocytosis?

2. Suggestions for term paper final drafts: Get another student or “four” to proof-read again just to double check your changes. • If you like I can put papers in my box at office…you can put one in to be edited and take one out to edit… do you want to voluntarily make this possible? Be sure each item in text relates specifically to your title, feel free to delete materials. Over all length of final draft “text” is reduced to 3 page minimum to help you, although making it longer than 3 pages is fine. Abstract vs. Conclusion: Make them differentthis is a tough one to do. • Brutal detail but short (no fluff) vs. Nice easy to read list/review of key points + a possible sentence or two about what the future of this sort of research will be/ Introduction: Tell the reader what topics you will discuss/teach and perhaps provide a bit of background info if really needed/ Try to have a minimum of two different references sources cited in each paragraph. Try for at least 3 sentences or 4 lines of text in each paragraph. Write to remove “fluff” (it hurts to take things out that represent “neat” info) that is not VERY specific to your paper “title”, if it does not relate to the title it probably should be removed With regards to content in paper you need to look for repeated items/info and please remember: REPEAT  DELETEor rephrase/reword

3. Cellular compartmentalization allows for local specialization in “eukaryotic” cells. [prokaryotes have NO organelles] • Endoplasmic reticulum: make protein, store calcium, metabolize drugs/glycogen • Double PL lipid membranes (lumen=cavity inside) • RoughER-protein synthesis • SmoothER-modification and metabolism • Golgi Apparatus: modify/export protein • Double PL lipid membranes (lumen=cavity inside) • Vesicles (exit) and Endosomes(entry): How does a cell move things in/out of the cell • Lumen inside a single PL membrane Important but not on test: • Lysosome: digest material inside cell • Peroxisome: digest long chain fatty acids and bacteria

4. RER is ONE WAY: 1) mRNA finds a ribosome on ER membrane: Protein created and sent into lumen- 2) Golgi Apparatus: Protein to 3 destinations: Plasma membrane Lysosome Secretory Vesicles Constituitive/Regulated Free Ribosome: is Another Way: 1) mRNA finds ribosome free floating in cytosol: >Protein created/released to cytosol >Protein to intracellular destination Huge holes in targets let protein enter targets: i.e. Nucleus, Mitochondria, Chloroplast “Porins” permit entry into organelle What are the two places where we use ribosomes to make a protein? Answer: Free Ribosome or ribosomes on rough endoplasmic reticulum RERHow do these two methods differ?

5. Option One: NucleusmRNA Ribosome:ERGolgi ApparatusTargetOption Two: NucleusmRNA Ribosome inCytosolCytosolPoresTarget

6. Many proteins are modified after translation inside the ER lumen, mostly at the more distal Smooth Endoplasmic Reticulum! • Sequences are clipped off: Insulin • Disulfide bonds may be added: Insulin • Carbohydrates may be added: N-CAMS • Amino Acids may be modified to modify protein conformation: Hydroxylysine/Hydroxyproline • Chaperone proteins may fold nascent protein into precise conformations: Hemoglobin • Additional Modifications often take place in the Golgi Apparatus

7. The smooth ER is devoid of ribosomes and helps modify proteins and metabolize drugs/toxins. Cytochrome P-450 reduces molecules with e- from NADPH to destroy carcinogens/toxins  System increases toxin solubility: water soluble toxins lost in urine  BASIC RXN: R-H+NADPH+H++O2R-OH+NADP+H2O Cells make P-450 if stimulus continues (P450 induction)! This cellular event explains why drug resistance develops over time: AIDS, Addiction, Alcoholism, and Toxic Resistance. Application: Kurt Cobain and Pentabarbital This is also why some beneficial drugs just stop working in cells!

8. The smooth ER also helps with calcium, lipid transport, and carbohydrate metabolism. Calcium can be stored in the SER • Some SER is rich in IP3-regulated channels/Ca-ATPase • Ca exits SER in response to IPS-second messenger • Special muscle SER is called “Sarcoplasmic Reticulum” • Tons of sarcoplasmic reticulum in cardiac/skeletal myocytes • Keep cytosolic Ca in micromolar concentrations at rest • SER enzymes regulate glycogen metabolism cAMP-dependent glycogen phosphorylase in SER breaks down glycogen in hepatocytes! GlycogenG-1-PG-6-P

9. All protein export roads lead to the Golgi Apparatus: a massive organelle that modifies and targets protein for export: SER>CisGolgi> MedialCisterna>TransGolgi>Export from PM

10. Most proteins move directionally towards the plasma membrane (Anterograde Tx) for secretion. Sometimes proteins can also move from PM back to ER (Retrograde Tx).

11. REGULATED EXOCYTOSIS explains how glucose transporters (GLUT) in a vesicle reach the PM following a meal and insulin release! 2nd Messenger Cascade: Insulin StimulatesTyrosineKinase >Kinase activated Phospholipase >Lipase releases IP3 into cytosol >IP3 opens SER Ca++-channels >Ca++ initiates V-fusion with PM >Vesicle carrying GLUT is now on PM >Glucose can enter the cell! >Blood Glucose Levels Go Down >Diabetic Don feels better again! Exocytosis : fusion of secretory vesicles with PMConstituitive Exo: happens at same rate all the timeRegulated Exo: occurs in response to a stimulus (Ca)

12. Receptor-mediated endocytosis permits a cell to pull large particles inside after binding to receptors that line ‘clathrin coated pits’!

13. How Does the AIDSs Virus get into our cells? Endocytosis allows coated vesicle entry into the cytosol! (Pathogen Escapes Immune System when inside the cell) • Clathrin and receptors are typically recycled back to the PM! • Clathrin has a triskelion-like shape! • Provides structure to pit and attachment point for intracellular scaffolding • Endocytotic vesicles may fuse with lysosomes to modify/digest vesicle contents! • Lysosomes are rich in acids and digestive enzymes • Contents in lysosome removed by diffusion, remnants removed by exocytosis! • Many bacteria, protozoan parasites and viral particles get access to a cell by locking to PM receptors (that’s how they get inside cells!) • Drugs may prevent of docking/cell infection!