More membrane trafficking Flashcards

1
Q

What are COPII vesicles made up of?

A

Sar1 GTPase
COPII coat
Carries newly synthesised proteins

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2
Q

What des COPI move through the golgi?

A

Newly synthesised proteins and retreived proteins. These are moved in an anterograde and retrograde direction

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3
Q

Where are proteins usually coated by clathrin

A

Newly made lysosomal proteins at the TGN
Most material taken up by endocytosis

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4
Q

Describe cranio-lenticulo-sultural dysplastia

A

Caused by a mutation in SEC23A, causing abnormal ER to golgi trafficking
Musculoskeletal issues
May have been issues with secretory pathway delivering collagen to the ECM

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5
Q

What do SEC23A and SEC24 bind to, regardless of wild type of mutant?

A

GTP1

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6
Q

How does COPII package procollagen (300-400nm)?

A

COPII vesicles are 60-80nm diameter
The COPII coat sorts procollagen into tubular structures which are modified for large cargo sorting

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7
Q

Describe the Rab family of GTPases

A

Member of the Ras superfamily
Cycles between membrane and cytosol
Involved in membrane and vesicular trafficking
Originally identified for being active in a vesicle-SNARE fusion

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8
Q

How do Rab-GTPs work in vesicles?

A

Recruit tethering proteins which wiggle into cytoplasm from the membrane to dock to the vesicle. This promotes SNARE assembly

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9
Q

What cascades allow cargo to move between organelles?

A

Rab cascades
Cargo moves from a Rab5 to Rab7 compartment

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10
Q

What can a missense of Rab7a lead to?

A

Charcot-Marie-Tooth 2B
Excessive activation
Reduced autophagic flux
Premature neurotrophine receptor degradation
Inhibition of neurite outgrowth

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11
Q

How does Legionella pneumophila utilise Rab1?

A

It creates an ER-like compartment

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12
Q

What is the role of the smooth ER

A

Site of lipid synthesis
Role in calcium storage

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13
Q

Describe the inter membrane contact site between ER and microtubules

A

The ER forms a loop around mitochondria with its tubules

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14
Q

Is there evience of the ER fusing with organelles?

A

No, it only has only contact sites

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15
Q

What is CLEM?

A

Correlative light and electron microscopy.
Allows fluorescence to be identified and correlated with EM.
This shows an ultrastructure not shown in light microscopy

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16
Q

What is tomography?

A

Imaging using a penetrating wave to build up 3D models of organelles.

17
Q

Describe some features of membrane contact sites

A

Ribosomes are excluded
Membranes are very close together (10-80nm)
ER contacts can be short or long-lived

18
Q

What proteins link two membranes together?

A

Tethers

19
Q

Describe tethers

A

Can be protein-protein or protein-lipid
Around 30nm
Inhibit fusion
Has a defined lipid proteome

20
Q

What tether transfers cholesterol?

A

Oxysterol binding protein (OSBP)
This is raft-like

21
Q

What do tethers provide platforms for?

A

Calcium mobilisation
Lipid transfer
Signalling
Organelle division

22
Q

How much calcium is there in the ER lumen compared to cytosol?

A

Cytosol- 0.1μm
ER lumen- 60-500μm
This is due to calcium taken up by the endocytic pathway

23
Q

What is the Stim1 receptor?

A

TM calcium sensor in the ER
Monomeric under resting conditions
When calcium levels fall, Stim1 is oligomerised

24
Q

What does oligomerised Stim1 interact with on the plasma membrane?

A

Ora1 channel
This is abundant in plasma membrane rich in PIP2

25
Q

How is cholesterol moved to plasma membranes?

A

Cholesterol sensors in the ER switch on its synthesis. LDL receptors take cholesterol, move through the endocytic pathway and are broken down in lysosomes, releasing free cholesterol

26
Q

What proteins move cholesterol through the cytosol?

A

Lipid transfer proteins (LTPs). Hydrophobic grooves to protect from the hydrophbic environment of the cytosol
Move along concentration gradients of lipids or ions

27
Q

Describe Niemann Pick C disease

A

Mutation in a TM protein important in contact sites.
Lipids accumulate in spleen, liver, lungs, bone marrow and brain
Sphingomyelin accumulates in lysosomes

28
Q

How are membrane contact sites involved with organelle fission?

A

ER surrounds fission enzymes acting on enzymes
MCSs interact these interactions

29
Q

Describe 2 diseases associated with MCS

A

TDP-43 is linked to ALS and regulates ER-mitochondria contacts
REEP1 is associated with hereditary spastic paraplegia, leading to disruption of the ER mitochondria contacts