Protein Trafficking Flashcards

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1
Q

different organelles in eukaryotic cells have distinct

A

PH and ionic compositions

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2
Q

eukaryotic cells are

A

highly organized with numerous specialized sub compartments

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3
Q

cellular anatomy

A

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

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4
Q

proteins produced

A

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

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5
Q

carrier proteins

A

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

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6
Q

default pathway for protein

A

cytosol unless tagged to go somewhere else

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7
Q

3 major mechanisms for protein targeting to organells

A
  1. Gated transport
  2. Transmembrane transport
  3. Vesicular transport
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8
Q

gated transport

A

cytosol nucleus

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9
Q

transmembrane transport

A

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

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10
Q

vesicular transport

A

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

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11
Q

Gated transport

A

nuclear localization signals (tagged to go to nucleus)

nuclear export signals (Tagged to leave nucleus)

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12
Q

How do nuclear import and export signals work?

A

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

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13
Q

calcineurin

A

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

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14
Q

clinical relevance NLS NES

A

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

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15
Q

transmembrane protein transport

A

example of mitochondrial import and cotranslational targeting into ER

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16
Q

vesicular transport

A

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

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17
Q

exocitic pathways

A

transport route from ER -> Golgi -> plasma membrane

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18
Q

endocytic pathways

A

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

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19
Q

vesicles

A

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

20
Q

budding

A

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

21
Q

fusion

A

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

22
Q

donor compartment

A

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

23
Q

acceptor compartment

A

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?)

24
Q

Glycoproteins

A

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

25
Q

major biosynthetic function of ER

A

covalent addition of sugar to protein

26
Q

addition of oligosacharides to protein

A

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

27
Q

N linked glycosylation

A

aids protein folding in the ER

28
Q

ER quality control

A

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

29
Q

ER protein folding and cystic fibrosis

A

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

30
Q

additional post translational modification after the ER

A

may take place in the Golgi

31
Q

n linked oligosacharides destined for plasma membrane

A

remodeled and terminate with silica acid residues

32
Q

N linked oligosacharides destined for lysosome

A

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

33
Q

differential post translational modifications

A

create appropriate signal for diverse destinations

34
Q

M6P groups

A

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

35
Q

lysosomal hydrolases in late endosomes

A

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)

36
Q

lysosomal storage disorders

A

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

37
Q

I-cell disease

A

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

38
Q

listeria monocytogenes

A

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

39
Q

endocytosis

A

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)

40
Q

different types endocytosis

A

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

41
Q

pathogens and endocytic pathways

A

pathogens can exploit endocytic pathways to get into cell

42
Q

hypercholesterolemia

A

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?

43
Q

homozygous familial hypercholesterolemia

A

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

44
Q

Clatharin mediated endocytosis

A

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

45
Q

role of differential pH in endosomal sorting

A

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

46
Q

lysosomes participate in

A

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

47
Q

creation of transport vesicles

A

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