Identification of microtubule growth deceleration and its regulation by conserved and novel proteins

Benjamin Lacroix1, Joël Ryan2, Julien Dumont3

  • 1Institut Jacques Monod, CNRS, UMR 7592, University Paris Diderot, Sorbonne Paris Cité, F-75205 Paris, France asm@unc.edu benjamin.lacroix@ijm.fr.

Insights

Scientists discovered novel proteins, cyclins-1 and -2, that regulate microtubule (MT) dynamics in smooth muscle cells. These proteins cause MT deceleration in the cell periphery by affecting tubulin concentration, revealing new insights into cytoskeletal regulation.

Area of Science:

  • Cell Biology
  • Cytoskeletal Dynamics
  • Molecular Regulation

Background:

  • Microtubules (MTs) are crucial cytoskeletal polymers involved in cell division, intracellular transport, and cilia/flagella formation.
  • MTs exhibit dynamic instability, characterized by growth, shortening, catastrophe, and rescue events, with parameters varying by cell type.
  • Previous work showed MT dynamic parameters change during smooth muscle cell differentiation in Caenorhabditis elegans.

Purpose of the Study:

  • To investigate local differences in MT dynamics within smooth muscle cells.
  • To identify molecular mechanisms underlying novel MT behaviors observed in the cell periphery.
  • To characterize the role of newly identified proteins in regulating MT dynamics.

Main Methods:

  • Live imaging of single microtubules in intact Caenorhabditis elegans smooth muscle cells.
  • Analysis of microtubule dynamic parameters, including growth rates and deceleration events.
  • Investigation of the role of novel cyclins (cylc-1, cylc-2) and ZYG-9(TOGp) in microtubule regulation.

Main Results:

  • A novel MT behavior, abrupt growth rate deceleration, was observed in the cell periphery.
  • MT deceleration correlates with decreased local soluble tubulin concentration.
  • Two novel proteins, cylc-1 and cylc-2, homologous to human cylicins and stathmins, regulate MT deceleration by affecting tubulin concentration.
  • ZYG-9(TOGp) mediates faster polymerization rates in the cell body.

Conclusions:

  • Local regulation of tubulin concentration by novel cyclins (cylc-1, cylc-2) drives MT deceleration at the cell periphery.
  • This study identifies two key molecular contributors to a novel microtubule behavior.
  • The findings provide new insights into the complex regulation of cytoskeletal dynamics in specific cellular compartments.

Related Concept Videos

Microtubule Instability02:17

Microtubule Instability

Microtubules are hollow cylindrical filaments having a diameter of approximately 25 nm and a length that varies from 200 nm to 25 μm. GTP-bound tubulin subunits form αβ-heterodimers for microtubule assembly. These core building blocks interact longitudinally, polymerizing into protofilaments. The protofilaments then interact with one another through lateral bonding forces to form stable cylindrical microtubules. These cylindrical filaments are dynamic as they undergo repeated...
6.4K
Microtubule Instability02:17

Microtubule Instability

6.1K
Destabilization of Microtubules01:45

Destabilization of Microtubules

The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
3.9K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.9K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
4.3K
Microtubule Formation01:23

Microtubule Formation

Microtubules are dynamic structures that undergo continuous assembly and disassembly. They originate from specialized multi-protein complexes known as microtubule organizing centers or MTOCs. Within the MTOC, the point of origin of the microtubule is known as the minus end, while the end radiating outward is the plus end. Microtubules serve two primary functions — the organization of spindle complexes to separate sister chromatids during mitotic or meiotic cell division and the formation...
8.1K