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?

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

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?

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:a) Plasma membraneb) Lysosomec) 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

Option One: NucleusmRNA Ribosome:ERGolgi ApparatusTargetOption Two: NucleusmRNA Ribosome inCytosolCytosolPoresTarget

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

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++O2R-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 PentabarbitalThis is also why some beneficial drugs just stop

working in cells!

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 metabolismcAMP-dependent glycogen phosphorylase in SER breaks

down glycogen in hepatocytes!GlycogenG-1-PG-6-P

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

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

Dynein and kinesin proteins can be active at the same time and move vesicles in opposite directions (- or +) on the same microtubules!

Exocytosis : fusion of secretory vesicles with PM Constituitive Exo: happens at same rate all the timeRegulated Exo: occurs in response to a stimulus (Ca)

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!

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

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!