Exam #1: Cell Biology IV Flashcards
How are phospholipids synthesized?
- Phospholipids are synthesized on the cytosolic monolayer
- Scramblase flips the phospholipids into the other monolayer, maintaining symmetry
Scramblase
- Flips phospholipids from on monolayer into another
- Maintains membrane monolayer symmetry
What happens when additional plasma membrane is no longer needed?
Macroautophagy
Phospholipid Exchange Protein
transfers phospholipids from the ER to another membrane in the cell
What is Atlastin?
- GTPase that is involved in constructing & shaping the ER
- ER scaffold protein
Atlastin Abundance
Increased ER membrane fusion & absence of Golgi
Atlastin Deficiency
- ER becomes fragmented
- Hereditary Spastic Paraplegia
Hereditary Spastic Paraplegia
- Caused by Atlastin deficiency
- Leg stiffness, gait disturbances, facial dysmorphia
Proteasome
- In BOTH cytosol & nucleus
- MOST are ubiquitin dependent, but NOT all
- Energy dependent
What are examples of things that are eliminated by proteasomes?
- Cyclin/CDKs (mitotic factors)
- CFTR
What disease states inhibit proteasome action?
- Prion proteins (Creutzfled Jacob Disease)
- Amyloid (Alzheimer’s Disease)
- Lewy Bodies (PD)
Bortezomib
- Proteasome inhibitor that is used in the treatment of multiple myeloma
- Decreases the degradation of pro-apoptotic factors i.e. causes an elevation of pro-apoptotic factors
Golgi Apparatus
- Situated near the nucleus
- Contains cisternae (sacs)
What are the functions of the Golgi Apparatus?
- Sorting proteins from the ER
- Protein modification
- Packaging of proteins into vesicles
- Movement of proteins through membranous compartments of the cell
Wilson’s Disease
- Defective copper transporter, ATB7B
- Causes a decrease in plasma ceruloplasmin
- Defective excretion of copper
- Copper is neurotoxic & also accumulates in the cornea
ATB7B
- Copper transporter that is embedded in the membrane of the Golgi
- Allows for movement of copper into the Golgi
- Also, allows for movement of copper into secretory vesicles that are eliminated in the bile
Ceruloplasmin
- Major copper-binding protein in the blood
- Binds copper in the Golgi apparatus & then excreted into the blood
Apoceruloplasmin
Copper not bound to binding protein
Kayser-Fleischer Ring
- Copper deposition in the cornea
- Sign of Wilson’s Disease
Dysferlin
- Microperforations occur in muscle cells during muscle activity
- Dysferlin protein is involved in “patching”
- Packaged in the Golgi
- Mutated in some forms of Muscular Dystrophy
Proinsulinemia
Normal:
- Pre-proinsulin is packaged & sent to the Golgi
- Golgi converts pre-proinsulin into proinsulin
- Golgi then packages proinsulin w/ enzyme that will cleave proinsulin into insulin
- Regulated Pathway
Pathologic:
- Proinsulin is mutated & missorted into the constitutive pathway
- Proinsulin converting enzyme is sorted into Regulated Pathway
- Misorting leads to an increase in proinsulin, proinsulinemia
Negative Golgi Image
- Light stained region next to the nucleus
- Cytoplasm is basophilic, but Golgi is not
- Gives negative image
Positive Golgi Image
- Golgi stained with heavy metal
- View electron dense profiles
- In nerve, Golgi encircles the nucleus
Cis Golgi Network
Receives vesicles from the ER
Trans Golgi Network
Secretes vesicles
Endosomal Compartments
- Near the cell membrane
- Early & recycling endosome
- Multivesicular Body
- Late endosome
Lysosomal Compartments
- Close to the interior of the cell
-
Early Endosome
- Located in the cell’s periphery
- pH 6.2-6.5
Recycling Endosome
- Just beneath the plasma membrane
- Store membrane proteins e.g. glucose transporters
- Insulin binding, insert glucose transporters into the plasma membrane
Multivesicular Body
- Deeper than early endosome
- Budd off the early endosome
- Transported along microtubules to late endosome
- pH 5.0- 6.2
- Origin of exosomes
Late Endosome
- Fuse with multivesicular bodies
- pH ~5.0
- Fuse with or mature into lysosomes
What controls the acidity of the endosomal and lysosomal compartments?
H+-ATPase
Fates of Endocytosed Receptors & Ligands
- Receptor is recycled & ligand is degraded- LDL
- Receptor & ligand are recycled- Transferrin
- Receptor & ligand are degraded- EGF
- Receptor & ligand are transported across cell & secreted (transcytosis)- IgA (secretory antibody)
What uncouples receptors & ligands when the receptor is recycled and the ligand is not?
Acidic pH of the early endosome
Achondroplasia
- Dwarfism
- Caused by abnormal recycling of the FGFR3 (fibroblast growth factor receptor) back to the surface of the cell
- Overstimulates & amplifys the signal, which ultimately leads to dwarfism
Transport of Lysosomal Hydrolases
- Lysosomal Hydrolase Precursor is tagged with mannose
- Cis–>Trans Golgi
- Mannose 6-phosphate receptor recognizes the mannose tag
- Delivered to endosome or lysosome
At what pH are lysosomal hydrolases most effective?
Low
What are the different pathways used to degrade material?
- Autophagic
What are the different autophagic processes?
1) Macroautophagy (organelles)
2) Microautophagy (protein)/ Chaperone-mediated autophagy
Heterophagosome
- Contains something that was brought in from the external environment to be degraded
- vs. autophagosome
Heterophagolysosome
- Heterophagosome fused with lysosome
- Secondary lysosome
Residual Body
- Material that could not be digested by the lysosome
- Forms lipofuscin
What is special about osteoclasts?
Secrete lysosomal hydrolyses for degradation of bone material
Primary Lysosome
- Not degrading anything/ has not received a phagosome
- Homogenous
Secondary Lysosome
- Fused with phagosome
- Degrading material
- Heterogenous (light & dark)
Pompe Disease
- Caused by a defect in the delivery of the lysosomal hydrolases to the lysosome
- Glycogen storage disorder, where glycogen accumulates in lysosomes
Tay-Sachs Disease
- Deficiency in the enzyme that breaks down sphingolipids
- Lipid material accumulates in lysosomes
- EM-level gives the lysosomes a “whirling” pattern
