Exam 2 pt2 Flashcards

1
Q

starts 7.3 slide 4

endolysosome lysosome and late endosome cycle

A
  • late endosome fuse with lysosome to create endolysosome
  • endolysosome digest contents to make lysosome
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2
Q

autophagy steps

A
  1. nucleation
  2. extension to form autophagosome
  3. fusion of autophagosome and lysosome
  4. digestion
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3
Q

M6P groups are added in

A

cis golgi

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4
Q

addition of M6P marker

explain process

A
  • lysosomal hydrolase with signal patch binds recogn site of GlcNAc phosphotransferase
  • UDP-GlcNAc binds catalytic site
  • transfer of GlcNAc to mannose residue on the hydrolase
  • release from phosphotransferase
  • GlcNAc removed
  • hydrolase with a M6P marker
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5
Q

Sorting signal attached to acid hydrolases destined for lysosomes

A

M6P

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6
Q

M6P receptor proteins are returned to the trans Golgi network via

A

retromer-coated transport vesicles

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7
Q

after hydrolase is marked with M6P what happens

explain process

A
  • M6P marker is recognized by receptor that binds it
  • clathrin coated vesicle buds off
  • fusion with early endosome, cargo and receptor in endosome
  • hydrolase cargo unbinds due to the pH being acidic
  • lysosomal acid phosphotase removes the phosphate so cargo cannot rebind receptor
  • receptor taken back in retromer coated vesicle
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8
Q

M6P receptors bind to M6P groups in pH _ in the _

A

pH 6.5-6.7 in the trans golgi

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9
Q

M6P receptors release M6P groups at pH _ in the _

A

pH 6, in the endosomes

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10
Q

M6P receptor protein contains…

A

a sorting signal recognized by the retromer complex

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11
Q

Lysosomal storage disease

A

Condition in which defects in lysosomal hydrolases cause an accumulation of undigested substances

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12
Q

Inclusion-cell disease (I-cell disease)

A

A severe type of lysosomal storage disease in which almost all hydrolases are missing from lysosomes, caused by a defect in GlcNAc phosphotransferase

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13
Q

Hurler’s disease

A

A type of lysosomal storage disease in which a hydrolase responsible for the breakdown of certain glycosaminoglycans is mutated or deleted

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14
Q

Lysosomal exocytosis

A

Process in which lysosomes fuse with the plasma membrane and secrete their contents into the extracellular space

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15
Q

Melanosomes

A

Specialized lysosomes that store pigments for eventual release by exocytosis

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16
Q

types of endocytosis

A
  • pinocytosis
  • macropinocytosis
  • receptor mediated endocytosis
  • phagocytosis
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17
Q

Pinocytosis

A

The continuous ingestion of plasma membrane and extracellular fluid by clathrin-coated or clathrin-independent vesicle formation

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18
Q

Process also known as pinocytosis

A

cell drinking

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19
Q

Macropinocytosis

A

Noncontinuous, clathrin-independent endocytosis triggered by the binding of specific ligands to cell-surface receptors

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20
Q

Receptor mediated endocytosis

A

Process in which specific, receptor-bound cargo is efficiently and rapidly taken into the cell by clathrin-coated vesicles

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21
Q

Phagocytosis

A

Process by which large molecules, microorganisms and cells are taken in from the cell exterior for delivery to lysosomes

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22
Q

cell eating

A

phagocytosis

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23
Q

phagocytic cells

A

Cells which specialize in the uptake of microorganisms, large particles and dead cells from the extracellular environment

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24
Q

_ regulates the protein composition of plasma membranes

A

recycling endosomes

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25
Q

Most endocytic vesicles fuse with _ , where _

A

early endosomes, where their cargo is sorted

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26
Q

The recycling pathway operates…

A

continuously, compensating for the constant loss of plasma membrane due to nonstop endocytosis.

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27
Q

Endosomes _ as they mature into late endosomes

A

begin to acidify their lumens

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28
Q

Membrane proteins destined for degradation are internalized in _ to form _

A

intralumenal vescicles to form multicesicular bodies

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29
Q

most cells _ within small pinocytotic vesicles

A

continuously ingest bits of plasma membrane and EC fluid

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30
Q

non clatherin pinocytosis is done by

A

caveolae

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31
Q

caveolae

A

Plasma membrane pinocytic invaginations lacking clathrin coats

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32
Q

some viruses use _ to infect _

A

use caveolae to infect endosomes, to the ER then the cytosol

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33
Q

macropinocytosis process

A
  1. activation of signalling receptor
  2. plasma membrane protrusion from actin rearrangement
  3. ruffle (protrusion) collapses
  4. vacuole closure
  5. this makes macropinosome (vesicle)

7.4 pg 8

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34
Q

receptor mediated endocytosis is better for _ than pinocytosis

A

uptake of specific molecules

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35
Q

cholestrol transport is an example of

A

receptor mediated endocytosis

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36
Q

LDL

A

Lipoprotein particles used to transport cholesterol in the blood

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37
Q

_ binds LDL to LDLR

A

apolipoprotein B

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38
Q

when cholestrol is required…

process

A
  • LDLr is made
  • LDLR binds to calthrin coated pits
  • LDLR and LDL vesicles go to endosome
  • LDLR are recycled back
  • LDL is broken down
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39
Q

defects in cholestrol uptake leads to

A

atherosclerotic plaques

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40
Q

3 possible fates of endocytosed receptors

A
  1. recycled
  2. transcytosis (moved)
  3. receptor down regulation (degraded)
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41
Q

receptor down regulation

def

A

Pathway used to destroy specific receptor by delivering them to lysosomes, resulting in reduced sensitivity to specific signaling molecules

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42
Q

in transcytosis,

A

molecules are transported from one cell domain across the cell into another domain

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43
Q

Macropinosomes acidify and fuse with_ , where _

A

late endosomes or endolysosomes, where cargo is degraded;

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44
Q

When recycling occurs, recycling transport vesicles…

A

bud from early endosomes and either return directly to the original plasma membrane domain, or make a stop at recycling endosomes

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45
Q

In the process of receptor down-regulation…

A

ubiquitin-tagged receptors are incorporated into the intralumenal vesicles of multivesicular bodies by the sequential binding of cytosolic ESCRT (Endosome Sorting Complex Required for Transport) complexes

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46
Q

phagocytosis can be carried out by

A

phagocytes like macrophages and neutrophils

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47
Q

Phagocytosis is triggered when…

A

when receptor molecules on the surface of phagocytic cells recognize
* antibodies
* complement components
* certain oligosaccharides on the surface of bacteria.
* phosphatidylserine on the surface of cells undergoing apoptosis

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48
Q

after receptor binding in phagocytosis…

A

Receptor binding induces the phagocyte to extend pseudopods which engulf the particle and fuse at their tips to form a phagosome.

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49
Q

_ shapes pseudopods

A

Localized actin polymerization

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50
Q

the _ regions of antibodies are recognized by _ receptors on the surface of _

A

Fc, macrophages and neutrophils

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51
Q

local actin polymerization that shapes pseudopods in phagocytosis is activated by

A

PI3 Kinase

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52
Q

constitutive secretory pathway

A
  • default pathway
  • proteins immediately and continuosly delivered to cell surface
  • no signal needed
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53
Q

Exocytosis may be _ or _

A

constitutive (i.e. continuous) or regulated (i.e. in response to a stimulus)

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54
Q

Proteins destined for the cell exterior will follow the constitutive pathway unless they

A
  • contain retrieval signals for return to the ER
  • are resident Golgi proteins
  • are tagged for delivery to endosomes/lysosomes
  • are involved in the regulated secretory pathway
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55
Q

signals which direct secretory proteins to aggregate are

A

not well defined and may be diverse

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56
Q

clatherin molecules are not present on _ secretory vescicles

A

mature, budded off

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57
Q

Secretory vesicles are formed in the _ in response to _

A

trans Golgi network in response to the aggregation of secretory proteins.

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57
Q

Secretory vesicles are formed in the _ in response to _

A

trans Golgi network in response to the aggregation of secretory proteins.

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58
Q

Immature secretory vesicles are initially formed by

A

Golgi membrane loosely wrapping around the protein aggregates

59
Q

In mature secretory vesicles, the lumenal pH

A

drops due to the action of V-type ATPases

60
Q

The high concentration in secretory vesicles enables

A

rapid release of large quantities of protein

61
Q

Some secretory proteins are synthesized in the ER as

2 things and which

A
  • inactive precursors (which must subsequently be cleaved for activation)
  • as polyproteins (which must be cleaved to release individual peptides).
62
Q

Polyprotein

A

Protein containing multiple copies of the same or several different signaling peptides; it must be cleaved to release the individual molecules

63
Q

synaptic vesicle fusion process

A
  1. docking (vesicle approaches)
  2. priming 1 (vesicle partially assembles SNAP or SNARE)
  3. priming 2 (complexin binds)
  4. fusion pore opening (when Ca up, synaptogabin activated and replaces complexin)
  5. fusion complete
64
Q

most synaptic vesicles after release

A

do not go back to the endosome, they are directly recycled as vesicle transporters and refilled immediately

65
Q

to not add to the membrane

A

an equal amount of exocytosis and endocytosis needs to occur

66
Q

examples when regulated exocytosis enlarges membrane

A

cytokinesis, phagocytosis, plasma membrane repair

67
Q

Epithelial cells have two distinct membrane domains…

A

the apical domain (faces internal lumen or outside environment) and basolateral domain (covers the remaining cell surface)

68
Q

Two processes are used to maintain distinct membrane domains:

A

(1) Membrane components are randomly delivered to a membrane domain, and then specific components are retained and/or removed from each domain; and
(2) Directed delivery of membrane components to appropriate membrane domain

69
Q

Mutations in any of the ESCRT proteins will prevent

A

the incorporation & destruction of receptors, causing them to be returned to the plasma membrane.

70
Q

The M6P receptor not binding to the clathrin vesicles would result in

A

the vesicle not being able to bud off the plasma membrane
This would mean that lysosomal hydrolases would fail to reach the endosomes.

71
Q

If the Sar1 protein is unable to bind to GTP then

A

it cannot insert itself into the cytoplasmic leaflet of the ER membrane. The binding of Sar1 and GTP recruits COPII adaptor proteins and regulates COPII-coated vesicular transport, so if the binding can’t occur then COPII coated vesicular transport from the ER would likely be reduced.

72
Q

T or F: Once a secretory vesicle is properly positioned beneath the plasma membrane, it will immediately fuse with the membrane and release its contents to the cell exterior.

A

false, it will wait for more signal

73
Q

Adenylyl cyclase

A

ATP to cAMP

74
Q

A-kinase anchoring proteins (AKAPs)

A

Proteins which bind the regulatory subunits of PKA to plasma membranes, nuclear envelope, mitochondrial outer membranes and microtubules

75
Q

Arrestins

A

Family of proteins which bind to phosphorylated GPCRs and participate in their desensitization by one of two mechanisms; (1) preventing the receptors from interacting with a G protein, or (2) serving as adaptor proteins to couple the receptors to clathrin-dependent endocytosis machinery

76
Q

Autocrine signalling

A

signaling cell same as target cell

77
Q

CaM-K is activated by and mediates

A

activated by calmodulin and mediates effects of increased cytosolic Ca2+

78
Q

calmodulin activates and is activated by

A

proteins, activated by rise in cytosolic Ca

79
Q

contact dependent signaling

A

Signaling process involving the interaction between membrane-bound signal molecules on the surface of one cell and receptor proteins on the surface of another cell

80
Q

Creb binding protein (CRB) activated by and activates

A

activated by CREB protein, binds to CRE and increases transcription

81
Q

_ activates CREB which activates _

A

PKA activates CREB which activates CBP -> CRE -> transcription

82
Q

cAMP phosphodiesterase

A

cAMP -> 5’ AMP

83
Q

CRE

A

Short sequences, found in many cAMP-regulated genes, which are bound by the regulatory CREB-CBP complex

84
Q

guanylyl cylase

A

GTP -> cGMP

85
Q

PKA activated by _ and does _

A

cAMP-activated enzyme which phosphorylates serines and threonines on target proteins

86
Q

desensitization

A

A decrease in a cell’s response to a stimulus due to prolonged exposure to the stimulus

87
Q

Effector protein

A

Protein which, when activated in an intracellular signaling pathway, implements changes in the cell’s behavior.

88
Q

effector protein examples

A
  • gene regulator proteins
    ion channels
    metabolic pathway things
89
Q

endocrine signalling

A

hormone

90
Q

GTPase-activating proteins (GAPs)

A

Proteins which regulate GTP-binding proteins by increasing the rate of GTP hydrolysis

91
Q

GEFs

A

promotes exchange of GTP for GDP, activate GTP binding proteins

92
Q

inhibitory g protein inhibits

A

adenylyl cyclase and decreases cAMP

93
Q

IP3 activated by and activates

A

relased from PIP2 which cleaved, opens ER Ca channels which increase Ca in cytosol

94
Q

IP3 - R

A

open in response to IP3, increase cytosolic Ca

95
Q

JAK-STAT signaling pathway

A

Signaling pathway activated by cytokines and some hormones, it provides one of the most direct routes from cell-surface receptors to gene regulation. In this pathway, cytosolic tyrosine kinases (JAKs) phosphorylate gene regulatory proteins (STATs)

96
Q

Kinase cascade

A

A signaling pathway in which a protein kinase is activated by phosphorylation, and in turn phosphorylates the next protein kinase in the sequence

97
Q

MAP kinase signaling module

A

An intracellular signaling pathway composed of three protein kinases acting in sequence (MAP kinase, MAP kinase kinase, and MAP kinase kinase kinase)

98
Q

NO synthase

A

Enzyme which catalyzes the deamination of arginine to produce nitric oxide (NO)

99
Q

Pleckstrin homology (PH) domains

A

Protein domain used by intracellular signaling proteins to bind PIP3

100
Q

Phosphoinositide 3-kinase (PI 3-kinase)

A

A kinase that phosphorylates inositol phospholipids at the 3 position of the inositol ring

101
Q

Phosphoinositide phosphatase

A

Enzyme which dephosphorylate PIP3

102
Q

_ activates PLC that _

A

Gq activates PLC which then cleaves PIP2 into IP3 and DAG

103
Q

Phosphotyrosine-binding (PTB) domains

A

domains on intracellular signaling proteins which recognize and bind to phosphorylated tyrosines

104
Q

PKC is activated by

A

Ca+, DAG and phosphatidylserine

105
Q

phosphotase

A

removes phosphate from AA of a protein

106
Q

Ras

A

A small, membrane-bound monomeric GTPase often required for the stimulation of cell proliferation or differentiation

107
Q

REceptor down regulation

A

Adaptation/desensitization to a stimulus which results from the receptor being endocytosed and destroyed in lysosomes.

108
Q

REceptor ser/threonine kinase

A

Enzyme-coupled receptors with a serine/threonine kinase cytosolic domain; ligands for these receptors include members of the transforming growth factor b (TGFb)-

109
Q

Receptor tyrosine kinase (RTK)

A

Enzyme-coupled receptors with cytosolic tyrosine kinase domains

110
Q

Receptor-activated Smads (R-Smads)

A

Latent gene regulatory proteins that are phosphorylated and activated by receptor serine/threonine kinases in response to TGFb binding

111
Q

Regulator of G protein signaling (RGS)

A

Alpha-subunit-specific GTPase-activating proteins (GAPs) which inactivate G proteins by increasing the rate of GTP hydrolysis

112
Q

Scaffold proteins

A

Proteins which bind to groups of interacting intracellular signaling molecules and organize them into signaling complexes

113
Q

SH2 domains

A

Highly conserved phosphotyrosine-binding domains found on intracellular signaling proteins. Proteins with these domains can bind to activated RTKs and any other intracellular proteins that have transiently phosphorylated tyrosines

114
Q

SH3 domains

A

Highly conserved proline-rich binding domains found on intracellular signaling proteins

115
Q

Transforming growth factor-b (TGFb) superfamily

A

Structurally related, dimeric, extracellular signal proteins which act as hormones or local mediator to regulate many developmental processes, promote tissue repair and regulate immune responses. These signal molecules act by binding to receptor serine/threonine kinases

116
Q

Tyrosine phosphatases

A

Highly specific enzymes which dephosphorylate tyrosine residues, making sure that tyrosine phosphorylation signals are short-lived and the level of tyrosine phosphorylation is low in resting cells

117
Q

Tyrosine-kinase-associated receptors

A

Enzyme-coupled receptors (e.g. cytokine receptors) which have no enzymatic activity of their own, but instead associate with cytoplasmic tyrosine kinases (e.g. JAKS) to relay a signal

118
Q

cell surface receptor signal molecules are

A

hydrophillic

119
Q

intracellular receptor signal molecules are

A

hydrophobic

120
Q

synaptic signaling is fast or slow

A

fast

121
Q

endocrine sig fast or slow

A

slow

122
Q

synaptic signalling or endocrine have higher affinity

A

synaptic

123
Q

synaptic signalling can use

A

the same signalling for many targets

124
Q

endocrine requires _ signal molecues

A

unique

125
Q

rapid responses involve

A

proteins already in target cell

126
Q

slow responses involve

A

changes in gene expression or synthesis of new proteins

127
Q

cell respond to signals in

A

predtermined ways

128
Q

signal transduction

A

extracell signals into intracell

129
Q

intracellular signaling proteins relay signals by

A
  • generating small intracellular mediators
  • activating next signaling in the pathway
130
Q

kinase

A

removes a phosphate

131
Q

GTP -> GDP does what

A

turn off trimeric g protein

132
Q

GAP increase

A

rate of GTP hydrolysis, turning off

133
Q

signalling complexes are more

A

efficient bc they are close together

134
Q

hyperbolic cell response

A

smooth and graded to concentration of moleculel

135
Q

sigmoidal response to signal

A

highest change in response at medium concentrations of signal

136
Q

bistable system

A

positive feedback so strong that system stays on even after signal is gone

137
Q

short delay negative feedback mean

A

initial response to signal is strong but goes down

138
Q

long delay in negative feedback means

A

response will oscillate between high and low

139
Q

G proteins are attached to and composed of

A
  • cytosolic leaf of plasma membrane
  • 3 units: alpha beta and gamma
  • alpha unite is a GTPase and binds GTP/GDP
140
Q

GPCR when bound acts as a

A

GEF and promote GDP -> GTP

141
Q

binding of GTP causes

A

alpha unit confor change, G protein released from GPCR, alpha unit seperate from beta-gamma complex

142
Q

what inactivates the g protein

A

RGS, which binds alpha subunite and acts as a GAP, promoting hydrolysis

143
Q

binding of cAMP to PKA

physical

A

binding of cAMP to regulatory subunit of complex PKA results in disassociation of the 2 catalytic subunits

144
Q

gene transcription alter pathway

A

GPCR → Gs → adynyl cyclase → cAMP cytosol → PKA → CREB protein → CBP → CREB+CBP bind to CRE → transcription

145
Q

Gq →

whole pathway

A

Gq → PLC → cleaves PIP2 into DAG and IP3

DAG → PKC

IP3 → gated Ca channels on ER → Ca cytosol → PKC

146
Q

mechanisms of keeping Ca low in resting cells

A
  • cytosol: Na/Ca exchanger, Ca pump
  • ER: Ca pump into
  • mitoch: Ca into with pump