lecture 8 Flashcards

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1
Q

Microtubule motor proteins

A

Dynein and Kinesin

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2
Q

What do microtubule motor protein do?

A

Transport membrane bound vesicles, proteins and organelles at expense of ATP

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3
Q

What direction do kinesins move cargo?

A

(+) end of microtubule - anterograde

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4
Q

What direction do dyneins move cargo?

A

(-) end of microtubule - Retrograde

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5
Q

What does kinesin family domain contain?

A
  • ATP binding site
  • Microtubule binding site of motor
  • Neck domain takes steps - connects motor domain to stalk domain
  • Cargo binding domain
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6
Q

Kinesin 1

A

Globular, bulbous region at one end of molecule - region enlarged when antibody that binds to motor domain is present

  • Head or feet hydrolyse ATP to generate energy for neck movement
  • Has a stalk, tail and binding site in foot
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7
Q

Kinesin 1 cargo transport

A
  • Each requires 1 ATP movement in neck
  • Cargo binding site
  • Anterograde
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8
Q

Describe the different kinesins types

A

Kinesin 1 (conventional) - 2 heads, stalks the same

Kinesin 2 (heterotrimeric) - head and stalks differ

Kinesin 5 (bipolar) - 4 head and stalks - sliding - mitosis to separate chromosomes

Kinesin 13 (KinI) - End disassembly

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9
Q

Describe the process of kinesin movement along microtubules

A
  1. Forward motor binds beta-tubulin, releasing ADP
  2. Forward head binds ATP
  3. Conformational change in neck linker causes rear head to swing forward
  4. New forward head releases ADP trailing head hydrolyses ATP and releases Pi
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10
Q

Catalytic core of kinesin is similar to catalytic core of what other molecule?

A

Myosin

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11
Q

Cytosolic dyneins

A
  • Retrograde (transport cargo towards - end of microtubule)
  • Very different structure to kinesins
  • Do have ATPase and microtubule binding domains
  • Linked to cargos by large complexes of microtubule binding proteins
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12
Q

Dynein structural components

A
  • ATPase domain (head)
  • Microtubule binding domain (stalk)
  • Dynactin binding domain (Stem)
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13
Q

Dynactin

A
  • Near domain hydrolyses ATP which generates a force
  • Results in far mT binding domain detaching and moving forward one step
  • Cargo binding domain - huge complex which includes dynamitin, CapZ, Arp1
  • Required for cargo attachment
  • P150glued - helps dynein attach to microtubule at start of transport process
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14
Q

What happens at the end of a microtubule?

A
  • Motor proteins hitch a ride back with cargo of other motor proteins
  • 600nm per second - centre to periphery of cell in 2-3 seconds
  • Sciatic nerve over 1m long in some people - days rather than hours
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15
Q

Tau tangles

A
  • Cause Alzheimer’s disease
  • Microtubule disintegrates with subunits falling apart
  • Causes tangled clumps of tau proteins
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16
Q

Cilia and flagella

A
  • Contain microtubules
  • 9+2 arrangement with 9 outer doublet microtubules and 2 central pair microtubules
  • 13-protofilament microtubule and 10-protofilament microtubule with each outer doublet
  • Central pair contains 13 protofilaments each
17
Q

What does cell movement depend on?

A

Axoneme bending

Movement requires bending – force generated by axonemal dyneins (ATP)

Crosslinking prevents sliding and results in bending

18
Q

Axonemal dynein

A
  1. Cargo binding domain permanently fixed to A tubule
  2. Force generated by ATP hydrolysis in heads
  3. Force attempts to slide
  4. Nexin crosslinks prevent sliding
  5. Wave like motion
19
Q

Nexin links

A

Microtubules slide past each other if:
- Nexin links removed by protease
- ATP provided

20
Q

3 types of microtubules in spindle

A

Kinetochore - Connect chromosomes and spindle poles via kinetochore attachment site

Polar - Overlap, Hold poles together, regulate pole-to-pole distance

Astral - Radiate from each spindle pole towards cortex of cell, position spindle and determine plane of cytokinesis

21
Q

Size of intermediate filaments

A

10-12nm

22
Q

Do intermediate filaments have motor proteins?

A

No

23
Q

What are intermediate filaments

A
  • Formed from family related proteins e.g. keratin or Lamin
  • Strong, ropelike structure
  • Provide nuclear membrane support or for cell adhesion
24
Q

5 classes of intermediate filaments

A

Class I - Acidic keratins - epithelial cells - tissue strength and integrity

Class II - Basic keratins - epithelial cells - tissue strength and integrity

Class III - Desmin (muscle) - Sarcomere
GFAP (glial cells) - Organisation
Vimentin (mesenchymal cells) - Integrity

Class IV - Neurofilaments - neurons - axon organisation

Class V - Lamins - nucleus - nuclear structure and organisation

25
Q

What do intermediate filaments do?

A
  • Mechanical support to plasma + nuclear membrane
26
Q

Why are intermediate filaments more stable than microfilaments and microtubules?

A

alpha helical rod structure of subunits which overlap along filament

27
Q

Basic structure of intermediate filaments

A
  • 10nm diameter filaments
  • Globular N-terminal and C-terminal domains connected by central helical core domain - Responsible for filament organization and interaction
  • Core domain conserved among all IFs - mediates dimer and tetramer formation
  • N and C terminals differ and therefore distinguish IFs
  • Parallel dimer then antiparallel tetramer
  • C terminals at both ends. N terminals in middle
28
Q

Protofibrils

A

Tetramer forms protofilament

Protofilaments form protofibrils

Protofibrils twist into rope like microfilament

29
Q

What di IFAPs do in IFs

A

Connect different intermediate filaments

30
Q

Medical importance of intermediate filaments

A
  • Markers for specific cell types e.g. stem cells
  • Mutation to IF genes can also result in diseases like Epidermolysis bullosa simplex - Mutation in keratin 14 gene