Microtubules

Front 1

Microtubule structure

Back 1

These are the largest cytoskeletal filament - 25nm diameter and composed of alpha beta tubulin heterodimers. Subunits are incorporated at the + end. These filaments have polarity and form rigid, hollow rods.

Front 2

Microtubule function

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The function is to provide structural support and form a dynamic scaffold for cellular organisation, positioning of organelles, intra-cellular movement, cell locomotion and chromosome separation during cell division.

Front 3

Microtubule assembly

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Microtubules are in a state of constant polymerisation and depolymerisation through addition and loss of tubulin to polymer ends. There are alternate cycles of growth/shrinkage. Assembly requires GTP to be bound to beta-tubulin and GTP is hydrolysed by beta-tubulin GTPase after incorporation into filament. Alpha beta tubulin is added to the + end.

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Microtubule disassembly

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GTP hydrolysis weakens tubulin binding affinity which favours shrinkage. Alpha beta tubulin is lost at the - end. Dynamic behaviour of microtubules varies based on cell type and stage of cell cycle its in. In differentiated neurones, for example, axonal microtubule turnover is slow (half life of several days) but in dividing cells, microtubules polymerise and depolymerise rapidly (half life of seconds - minutes).

Front 5

Intracellular movement

Back 5

Microtubules act like highways in cells for vesicles, organelles etc to be transported. Main motor proteins involved in this transportation along microtubules include dyneins and kinesins. Microtubules are usually oriented with the - end anchored in the centrosome and + end extending towards periphery of cell.

Front 6

Dyneins

Back 6

These have globular heads with ATPase activity, the head walks along the microtubule and the tail binds toe cargo, moving it towards the - end of the microtubule (cell centre).

Front 7

Kinesins

Back 7

Different members of dynein and kinesin transport organelles in different directions. Kinesins are the same as dyneins but move cargo toward the + end of the microtubule (cell periphery).

Front 8

Cell locomotion

Back 8

This is the sliding of outer doublets relative to one another, and is powered by axonemal dynein. The movement of dynein head groups towards the - end causes bending of cilia/flagella and results in beating. Cilia are larger and have back/forth motion, flagella have wave like motion. Cilia move EC material and flagella move EC material plus the cell itself.

Front 9

Cell division

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The centrosome moves to opposite ends of cell and microtubules extend outwards, forming mitotic spindle. This results in the separation and distribution of chromosomes to daughter cells and determines intracellular organisation of microtubules involved in cell division.

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Microtubules involved in cell division

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Interpolar microtubules overlap at the centre of the cell, and astral microtubules go outwards towards the periphery. Kinetochore microtubules are attached to condensed chromosomes which stabilise microtubules.

Front 11

Chromosome separation

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In early mitosis the microtubules search and capture kineothcores and bind to 20-25 microtubules that emanate from a single spindle pole. Microtubules constantly detach and reattach as they are error prone. If not corrected, this impairs proper movement of segregation - chromosomal instability in cancer cell lines.

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Microtubule diseases

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Neurodegenerative - ALS & Alzheimers.

MS - neuroinflammatory disease.

Chediak-higashi - defect in microtubule polymerisation.

Ciliopathies - associated with cilia.

Cancer - chromosomal instability = increased rate of chromosomal segregation.

Joubert syndrome.

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Joubert syndrome

Back 13

This is a brain abnormality that results in decreased muscle tone (hypotonia), uncontrolled eye movement (nystagmus), absence/reduced voluntary purposeful eye movement (oculomotor apraxia), developmental delay and variable intellectual impairment, and episodes of apnoea and hyperapnoea.