Protein Trafficking

Question 1

different organelles in eukaryotic cells have distinct

Answer 1

PH and ionic compositions

Question 2

eukaryotic cells are

Answer 2

highly organized with numerous specialized sub compartments

Question 3

cellular anatomy

Answer 3

dynamic, protein traffic is required to maintain and establish compartmental identity

Question 4

proteins produced

Answer 4

on ribosomes, all proteins have a recognition motif (linear peptide or more complex motif)

Question 5

carrier proteins

Answer 5

recognize signal sequence/ signal patch/ post-translational modification; carrier proteins then facilitate transport to appropriate organell

Question 6

default pathway for protein

Answer 6

cytosol unless tagged to go somewhere else

Question 7

3 major mechanisms for protein targeting to organells

Answer 7

1. Gated transport
2. Transmembrane transport
3. Vesicular transport

Question 8

gated transport

Answer 8

cytosol nucleus

Question 9

transmembrane transport

Answer 9

cytosol -> mitochondria
cytosol -> ER
cytosol -> peroxisomes

Question 10

vesicular transport

Answer 10

ER golgi
Golgi late endosome ->lysosome
Cell surface-> early endosome -> late endosome -> Golgi -> ER
OR cell surface -> early endosome -> late endosome ->lysosome

ER -> Golgi -> cell surface
ER -> goligi -> secretory vesicle -> cell surface

Question 11

Gated transport

Answer 11

nuclear localization signals (tagged to go to nucleus)

nuclear export signals (Tagged to leave nucleus)

Question 12

How do nuclear import and export signals work?

Answer 12

with nuclear important and export receptors proteins or protein complexes that act as taxis to ferry cargo into and out of nucleus; export and import receptors can interact with cargo directly or indirectly and mechanism may be regulated

Question 13

calcineurin

Answer 13

phosphitase that induces signal transduction cascade activates transcription factor in cytoplasm with NLS which is masked with phosphorylation when phosphatase is active it dephosphorylates the NLS and this can then go to nucleus and activate gene transcription

Question 14

clinical relevance NLS NES

Answer 14

drug to block major nuclear export receptor now in trials for canine cancer

Question 15

transmembrane protein transport

Answer 15

example of mitochondrial import and cotranslational targeting into ER

Question 16

vesicular transport

Answer 16

organelles of secretory and endocytic system connected by vesicular transport; exocitic and endocictic pathways and transport vesicles all play a role

Question 17

exocitic pathways

Answer 17

transport route from ER -> Golgi -> plasma membrane

Question 18

endocytic pathways

Answer 18

route from plasma membrane through early and late endosomes to lysosomes; involved in internalization of material from extracellular space

Question 19

vesicles

Answer 19

transport vesicles carry material btwn compartments of exocytic and endocytic pathways; these vesicles must be selective in composition

Question 20

budding

Answer 20

vesicle pinching off from donor membrane containing correct cargo; involved in all vesicular transport

Question 21

fusion

Answer 21

membrane of vesicle merges with acceptor membrane of intended target; involved in all vesicular transport; this is regulated and shows specificity

Question 22

donor compartment

Answer 22

buds membrane-bound transport vesicles that carry cargo destined for acceptor compartment

Question 23

acceptor compartment

Answer 23

receives cargo from one or more donor compartments by fusion of incoming membrane-bound transport vesicle carrying cargo (appears to also be called target compartment sometimes?)

Question 24

Glycoproteins

Answer 24

majority of proteins that transverse the secretory and endocytic systems are modified in the ER with N-linked glycosylation; N linked oligosacharides are most common type oligosacharies found on glycoproteins

Question 25

major biosynthetic function of ER

Answer 25

covalent addition of sugar to protein

Question 26

addition of oligosacharides to protein

Answer 26

aids protein folding and can act as molecular tag to facilitate protein transport

Question 27

N linked glycosylation

Answer 27

aids protein folding in the ER

Question 28

ER quality control

Answer 28

Protein folding prerequisite for protein to be allowed to exit the ER and access secretory and endocytic system

Question 29

ER protein folding and cystic fibrosis

Answer 29

mutant form of CFTR (gene codes for ion channel) at ΔF508 does not fold correctly and is subject to quality control and is therefore not allowed to exit ER this results in effect in chloride and water transport

Question 30

additional post translational modification after the ER

Answer 30

may take place in the Golgi

Question 31

n linked oligosacharides destined for plasma membrane

Answer 31

remodeled and terminate with silica acid residues

Question 32

N linked oligosacharides destined for lysosome

Answer 32

modified by becoming phosphorylated on mannose residue (M6P); enzyme that performs this modification is N-acetylglucosamine phosphotransferase

Question 33

differential post translational modifications

Answer 33

create appropriate signal for diverse destinations

Question 34

M6P groups

Answer 34

recognized by transmembrane M6P receptor proteins present in trans Golgi network; receptor proteins bind to lysosomal hydrolases on lumenal side of membrane and to coat proteins on cytosolic side; they help package hydrolayses into clatharin coated vesicles that bud from transgolgi network; vesicles then deliver to late endosome and ultimately lysosome

Question 35

lysosomal hydrolases in late endosomes

Answer 35

dissociate from M6P receptor; M6P receptor binds proteins at pH6.5-6.7 in trans Golgi network and release at pH of 6 (pH of interior of late endosomes)

Question 36

lysosomal storage disorders

Answer 36

disease group of about 50 genetic disorders resulting from defect in lysosomal function usually due to deffect in enzyme required for hydrolysis of macromolecules

Question 37

I-cell disease

Answer 37

rare form of lysosomal storage disease that impacts all lysosomal enzymes (aka Mucolipidosis II;Inclusion-cell disease); caused by mutations in N-acetlyglucosamine phosphotransferase results in complete failure to identify hydrylytic enzymes in Golgi on route to lysosomes so these end up going to plasma membrane and ultimately end up in the blood; autosomal recessive, relevant to DSH

Question 38

listeria monocytogenes

Answer 38

example of how pathogen can exploit the endocytic pathway by utilizing endocytosis to get into cytosol, must break membrane open to get into cytosol prior to ending up lysosome where it would get broken down

Question 39

endocytosis

Answer 39

trafficking route that leads from plasma membrane inside of cell; this helps cell acquire nutrients and other molecules; internalization of surface receptors (signal transduction and maintenance of cell surface, such as apical and basolateral surfaces of polarized cells)

Question 40

different types endocytosis

Answer 40

phagocytosis (also critical function in development), pinocytosis, caveolae, and clathirin mediated endocytosis

Question 41

pathogens and endocytic pathways

Answer 41

pathogens can exploit endocytic pathways to get into cell

Question 42

hypercholesterolemia

Answer 42

possible cellular itinerary of molecules during endocytosis is an example of hypercholesterolemia; trafficking of LDL receptor via endocytosis is critical for animal cholesterol homeostasis and animals with this disease have defective LDL receptors?

Question 43

homozygous familial hypercholesterolemia

Answer 43

rare genetic disorder related to deffective LDL receptors which allows LDL to enter cell leading to deposition

Question 44

Clatharin mediated endocytosis

Answer 44

discovered because of homozygous familial hypercholesterolemia; LDL particles endocytosed by association with LDL receptor at cell surface; LDL receptor delivers cargo to lysosome and is then recycled for additional round of transport

Question 45

role of differential pH in endosomal sorting

Answer 45

pH differences of internal compartments can be exploited to facilitate intracellular transport

Question 46

lysosomes participate in

Answer 46

autophagy, (organelle quality control); lysosome fuses with autophagosome de novo organelle recruited to provide quality control for cellular organelles

Question 47

creation of transport vesicles

Answer 47

different types transport vesicles defined by different coats; coats ultimately responsible for cargo selection and generation of transport vesicle