LECTURE 3 - MICROFILAMENTS Flashcards
Describe the structure of microtubules
Microtubules are composed of α- and β-tubulin heterodimers assembled into a hollow, tube like cylinder.
Both α- and β-tubulin bind GTP, but only β-tubulin can hydrolyze GTP to GDP and later exchange GDP for GTP.
When bound to GTP, these tubulin dimers can assemble into microtubules.
Provide several examples of the roles of microtubules within the cell.
Providing structure and support for the cell.
Creating highways for intracellular transport.
Separating chromosomes during cell division.
Allowing for cellular movement through cilia and flagella.
Microtubule Polarity
tubulin dimers assemble head-to-tail, giving microtubules structural polarity:
α-tubulin at the (−) end
β-tubulin at the (+) end
The (+) end grows faster than the (−) end.
Role of MTOCs (Microtubule Organizing Centers)
MTOCs are structures that nucleate (start) and organize microtubules.
Most microtubules originate from an MTOC at the (−) end.
Typical cells have one MTOC, but mitotic cells have two, and some specialized cells may have many.
Microtubules are nucleated from γ-tubulin ring complexes in the pericentriolar material of MTOCs.
These ring complexes act as templates for αβ-tubulin dimers to start building the microtubule.
Dynamic Instability – GTP Cap Model
Microtubules constantly switch between growth and shrinkage – called dynamic instability.
Growth occurs when GTP-tubulin adds to the + end, forming a stabilizing “GTP cap”.
Once added, GTP is hydrolyzed to GDP, forming GDP-tubulin, which is less stable.
If GDP-tubulin is exposed at the tip (e.g. if GTP addition slows or stops), the microtubule becomes unstable and rapidly shrinks (catastrophe).
If new GTP-tubulin is added again, a new GTP cap can form, and growth resumes (rescue)
Medical importance microtubule-binding drugs
Microtubule/tubulin-binding drugs are used to treat a variety of diseases, including gout, certain skin and joint diseases, and cancer.
Such drugs either prevent microtubule assembly (e.g., colchicine) or prevent microtubule disassembly (e.g., the cancer drug taxol used for ovarian cancer, breast cancer and lung cancer)
Although the effects are opposite, the results are the same: inhibition of cellular processes that depend on microtubules and the dynamic rearrangement of these polymers.
What is the role of Microtubule-Associated Proteins (MAPs) and give some types
proteins that bind to microtubules to regulate their stability, growth, and organization within the cell.
Stabilizing MAPs
+TIPs (Plus End Tracking Proteins)
Destabilizing MAPs
Explain Stabilizing MAPs
These proteins promote microtubule assembly and increase their stability.
Some stabilizing MAPs can also crosslink microtubules into bundles.
Two important examples:
MAP2 – commonly found in dendrites of neurons, helps maintain microtubule spacing.
Tau – found in axons, promotes microtubule stability and spacing.
Explain Destabilizing MAPs
These proteins promote microtubule disassembly and help control microtubule turnover.
Kinesin 13
Binds to microtubule ends and promotes disassembly, helping shorten microtubules.
Stathmin
Binds to curved protofilaments (the shape seen during disassembly).
Enhances microtubule shrinkage by stabilizing the curved (unstable) form, making it easier for tubulin to come off.
