Microtubules are key players in cell structure and function. These hollow tubes, made of tubulin proteins, provide support, enable transport, and drive cell division. Their dynamic nature allows rapid assembly and disassembly.

Microtubules work with various proteins to carry out their roles. Motor proteins move cargo along microtubules, while other proteins regulate growth and stability. Understanding these interactions is crucial for grasping cellular processes.

Microtubule Structure and Dynamics

Structure and function of microtubules

• Microtubules are hollow, cylindrical structures composed of α-tubulin and β-tubulin heterodimers that arrange in a head-to-tail fashion to form protofilaments (13 protofilaments associate laterally to form a microtubule with a diameter of about 25 nm)
• Major component of the cytoskeleton that provides structural support and shape to the cell, serves as tracks for intracellular transport (vesicles, organelles), and plays a crucial role in cell division (mitotic spindle) and organelle positioning (Golgi apparatus, endoplasmic reticulum, mitochondria)

Microtubule polymerization and regulation

• Microtubule polymerization occurs through the addition of GTP-bound tubulin dimers to the growing (+) end, with GTP hydrolysis to GDP occurring shortly after incorporation, creating a GTP cap at the (+) end that stabilizes the microtubule and promotes further polymerization
• Depolymerization occurs when the GTP cap is lost, exposing GDP-tubulin at the (+) end, which has a lower affinity for the microtubule lattice, leading to rapid shrinkage (catastrophe)
• Microtubule dynamics are regulated by associated proteins, including microtubule-associated proteins (MAPs) that stabilize microtubules and promote polymerization, stathmin and other destabilizing factors that promote depolymerization, and end-binding proteins (EBs) that track the growing (+) end and regulate microtubule dynamics

Microtubule Functions and Associated Proteins

Roles in cellular processes

• Cell division
  1. Microtubules form the mitotic spindle, which separates chromosomes during mitosis and meiosis
  2. Kinetochore microtubules attach to chromosomes and pull them apart
  3. Astral microtubules help position the spindle and anchor it to the cell cortex
• Intracellular transport
  • Microtubules serve as tracks for motor proteins to transport vesicles, organelles, and macromolecules, with kinesins generally moving towards the (+) end (anterograde transport) and dyneins moving towards the (-) end (retrograde transport)
• Organelle positioning
  • Microtubules help position and maintain the location of organelles within the cell, such as the Golgi apparatus, endoplasmic reticulum, and mitochondria

Key proteins of microtubule dynamics

• Tubulin
  • α-tubulin and β-tubulin form heterodimers that polymerize to create microtubules
  • γ-tubulin is involved in microtubule nucleation at the centrosome
• Microtubule-associated proteins (MAPs)
  • MAP1, MAP2, and tau stabilize microtubules and promote polymerization
  • MAP4 is involved in microtubule bundling and stability
• Motor proteins
  • Kinesins are (+) end-directed motors involved in anterograde transport (vesicles, organelles)
  • Dyneins are (-) end-directed motors involved in retrograde transport and spindle positioning
• Other proteins
  • End-binding proteins (EBs) track the growing (+) end and regulate microtubule dynamics
  • Stathmin promotes microtubule depolymerization by sequestering tubulin dimers
  • XMAP215 and CLASP promote microtubule polymerization and stabilization