Flashcards in Cell IV Deck (113):
Where is the principle site of phospholipid synthesis?
CYTOSOLIC layer of sER
How do phospholipids get from the sER to anywhere else in the cell?
What is the action of phospholipid translocators?
catalyze the flip-flop of phospholipids from one monolayer to the other
Where are phospholipid translocators found?
membrane-bound enzymes in the sER
Where is Ca stored?
What is the function of atlastin?
a GTPase is involved in constructing and shaping the ER
What happens when there is over-expression of atlastin?
increased ER, lack of golgi
What happens where there is too little atlastin?
ER becomes fragmented
What disease has a deficiency of Atlastin been linked to?
Hereditary spastic paraplegia.
Symptoms include leg stiffness and gait disturbances such as stumbling and tripping. This is due to difficulty in hip flexion and dorsiflexion of the foot.
What are proteosomes?
Large proteases that require ATP
Where are proteosomes located?
In the cytoplasm and the nucleus
What are the three functions of proteosomes?
1. Regulating proteins in cell cycle
2. Malformed, denatured and damaged proteins
3. Antigenic proteins
What are the two major types of proteosomes?
Ubiqitin dependent and not (cytosolic is dependent)
True or false: prion proteins inhibit proteosomes?
Defective ubiquitination of proteins is implicated in what disease?
How are proteosomes implicated in cystic fibrosis?
destroy a competent but slow to fold CFTR
How can proteosomes contribute to CA?
Inhibition of them decreases the degrading of pro-apoptotic factors
Partial inhibition of proetosomes by bortezomib has been effective against what disease? How does this work?
Inhibits the over destruction of pro-apoptotic factors
What is the main function of the Golgi complex?
Functions as a major sorting and distribution center
How are proteins sorted in the golgi?
By their 'chemical zip code" (AA or carb attachments)
What are the five ways of protein modification in the Golgi?
Proteolytic cleavage of proteins
How are proteins sent out of the golgi?
Where is the golgi usually found?
Near the nucleus
How many cisternae usually comprise the Golgi?
What is the side of the golgi that faces the nucleus called?
Where do most of the transport vesicles to the golgi come from?
from the ER
How do proteins get to one Golgi stack to the next?
What is the side of the Golgi that faces the plasma membrane called?
The trans face
What is Wilson's disease?
An autosomal recessive disorder caused by a mutation in a protein pump for copper in the trans-Golgi network of liver cells. This results in impaired biliary excretion of copper.
How are proteins inserted into the membrane?
Via a start transfer and stop transfer sequence on the protein
Where is Ca stored in the cell?
What are three deleterious effects of elevated Ca levels in the cell?
What is the enzymes that flips phospholipids from the cytosolic side to the ER lumen side?
What is the enzymes that is required for ER building?
Where are proteosomes found?
In the cytoplasm and nucleus
True or false: proteosomes are ATP dependent
What is the transporter of Cu in the Golgi?
how are microperforations of skeletal muscles sealed?
Via membrane protein from Golgi in-transporting vesicles containing dysferlin.
What is dysferlin transport dependent on?
Deficiency of dysferlin are found in what three diseases?
three types of muscular dystrophy: Miyoshi myopathy, limb-girdle muscular dystrophy type 2b, and distal myopathy tibialis anterior muscle onset
What is the protein in the Golgi that holds the Cu?
Ceruloplasm (apoceruloplasm if not bound to Cu)
How is Cu excreted from cells
Via transport vesicles that are filled from ATP7B action
A defective Cu transporter (ATP7B) leads to what disease?
What are Kayser-Fleisher rings?
Cu rings around the eye found in Wilson's disease
Where is ceruloplasm found?
What happens to ceruloplasm levels when there is a defective Cu transporter?
What is the protein that is used in microtears of muscles? What type of diseases are defects of this protein implicated in?
How is insulin made/secreted? (3 steps)
First made into preproinsulin in the ER, and shipped to golgi.
Golgi forms vesicle with enz to cleave pro part inside.
These vesicles are held in the regulated pathway.
What is proinsulinemia?
A disease where mutated proinsulin is sent into the constitutive pathway, but prohormone secreting enzymes are secreted in the regulated pathway. (no insulin produced)
What stain is used to show a negative of the Golgi? Why does this work?
A basophilic stain (hematoxylin). Golgi is not charged.
How do you get a positive stain of the Golgi?
Where are the golgi found in nerve cells?
Completely surround the nucleus
You see a nucleus that is relatively clear on the EM. What can you infer based on this?
Transcription is taking place at high rates
What are endosomes?
dynamic membrane-limited compartments that exist in the cell’s cytoplasm. The organelles are involved in sorting and identifying molecules for recycling or degradation in lysosomes.
What are the four types of endsomes?
1. Early endosomes
2. Recycling endosomes
3. Multivesicular bodies
4. Late endosomes
Where are early endosomes located?
the cell's periphery
What is the pH of early endosomes?
6.2 - 6.5
How are endosomes acidified?
What are multivesicular bodies (MVBs)?
Small membrane bound structures from the early endosome located between the early and late endosome (transporter)
What is the pH of the multivesicular bodies?
How do MVBs get from the early to late endosome?
Via a microtuble
Where do the MVBs eventually go?
Mere with a late endosome or excreted (=exosomes!!)
What are late endosomes?
A permature lysosome that receives components for degradtaion from the early endosome.
Where are the late endosomes located?
Near the golgi
What is the pH of the elate endosomes?
What is the fate of a late endosome?
become a lysosome or merge with one
What is the function of the recyling endosome?
Bring transport molecules (like GLUT4) to the surface plasma membrane in response to a signal (insulin)
LDL receptor are endocytozed via clatharin coated pits and turned into what?
What happens to the LDL and receptors that are endocytozed (2)?
1. both brought to the early endosome where receptor is taken off of LDL and recycled back.
2. LDL goes to lysosome
What is the binding protein for Fe? What is the receptor? What process of endocytosis does the receptor/ligand go through?
2. transferrin receptor
3. Clatharin-mediated endocytosis
What causes the abnormal bone growth in achondroplasia
lysosomal targeting is disturbed due to a mutation of FGFR3 (fibroblast growth factor receptor). This causes FGFR3 to be recycled to the membrane rather than degraded
Why do you want to degrade receptor molecules after they have bound their ligand?
Stop over signalling
What is transcytosis?
Receptor and ligand are transported across the cell via endosomes
What cells use transcytosis?
What is the signal that is attached to the lysosomal hydrolase precursor?
How are lysosoms directed to the early endosome?
Mannose phosphate receptor on the last part of the golgi accepts and clatharin coats the vesicle. Now a receptor driven vesicle
What are inside of lysosomes?
True or false: enzymes are able to only able to destroy a tiny fraction of biological molecules?
False--most are able to be digested
In what type of cells are lysosomes primarily found?
professional phagocytic cells such as neutrophils and macrophages
How is the acidic nature of the lysosomes maintained?
What is the autophagic pathway?
Pathway where lysosomes degrade defective organelles
What are the three types of autophagy?
Chaperone-mediated direct transport
True or false: organelles destined for destruction are delivered to the lysoosome inside a membrane?
What is the term that describes the degradation of outside material such as bacteria?
What happens when sER is no longer needed?
Autophagy of the sER
What type of structure are eliminated via macroautophagy?
What type of structure are eliminated via MICROautophagy?
Proteins, small molecules
What molecules are needed to direct proteins to the lysosome?
What is a heterophagosome?
Phagosome what has foreign material in it
What are residual bodies?
Material that lysosomes cannot digest and leaves undegraded --accumulates
What is lipofuscin?
Build up of residual bodies
Are lysosomes acidophilic or basophilic?
Acidophilic (H+ in it)
What are Heterophagolysosomes?
primary lysosome + heterophagosome
What are the two destinies for digested material by lysosomes?
A lysosome that has consistent coloration throughout (on EM) is of what type?
A lysosome that has inconsistent coloration and a large, darker area (on EM) is of what type?
What is Pompe disease?
Glycogen storage disease due to M6P receptor
What is Tay-Sach's disease?
Problem with the breakdown of lipids
You're looking at a lysosome through EM and see a whorl effect. You also see a sample from the same tissue using light microscopy and E&M staining, that shows a very large, rounded area in the cell that appears white. What is your diagnosis?
How do integral membrane proteins establish themselves in the membrane?
1. There are start and stop sequences on the protein that are recognized by a translocator protein that starts and stops translocation of the protein as necessary.
2. a signal peptidase again cuts off the signal sequence
What are the four possible fates of endocytozed receptor and ligands? (Give examples of each)
1. Receptor is recycled and ligand is degraded (LDL)
2. Receptor and ligand are recycled (Fe)
3. Receptor and ligand are degraded (EGF)
4. Transcytosis [Receptor and ligand transported across the cell] (IgA)
Why would the cell want to degrade receptors? What happens in achondroplasia?
1. To stop signalling
2. FGFR3 is recycled instead of degraded
What is the sorting place for all of the receptor/ligands that are endocytozed?
What is the enzyme deficiency in Pompe's disease? What accumulates?
What is the enzyme defciency in GM1 gangliosidosis?
GM1 ganglioside beta-galactosidase
What is the enzyme that is deficient in Tay-Sach's disease? What accumulates?
Hexosaminidase a subunit
GM2 gangliosides accumulate
What is the enzyme that is deficient in Sandhoff (GM2 sphingolipidosis)? What accumulates?
GM2 gangliosides globosides
What is the defective enzyme in metachromatic leukodystropy? What accumulates?
What is the defective enzyme in Gaucher's disease? What accumulates?
What is the defective enzyme in Hurler disease? What accumulates?
Dematan sulfat, heparan sulfate
You are looking at a cell that has intense acidophilia of the cytoplasm, as well as an empty area outside the cell. What type of cell is this?
Osteoclast. (lysosomes are acidophillic)
You are looking at a muscle cell at note that there are large white areas where the contractile filaments should be. Using PAS, a sample from the same tissue demonstrates a deep magenta coloration. What is your diagnosis?
Pompe's disease (glycogen accumulating in muscle cells leaves no room for contractile filaments)