30.11:
Cytoskeletal Coordination in Cell Migration
Cell migration is a complex process that requires precise coordination between different cellular components, particularly the cytoskeleton which comprises actin filaments, microtubules, and intermediate filaments.
During migration, actin filaments are dynamically reorganized at the cell periphery and help establish the cell’s leading and trailing edges.
This polarity directs the centrosome, a microtubule organizing center, to position itself in front of the nucleus and orient the growing microtubules towards the leading edge.
The kinesin motors carry various cargo on these microtubule tracks, including exocytic vesicles containing integrins and new membrane components, actin remodeling proteins, and intermediate filaments.
The intermediate filaments stabilize and promote maturation of the newly formed focal adhesions.
At the trailing edge, the focal adhesions are disassembled, and the dynein motors carry the endocytosed integrins along the microtubules towards the leading edge for recycling.
Additionally, the cytoskeletal components are cross-linked to each other, and other organelles via linker proteins.
These cross-bridges enable the cytoskeletal components to synchronize their polarity and form a cohesive network for cell migration.
30.11:
Cytoskeletal Coordination in Cell Migration
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker proteins that form cross-bridges between the components. For example, the linker protein spectraplakin bridges microtubules with actin filaments, and KASH proteins link the nucleus to the cytoskeleton. Indirect communication is mediated via signaling cascades, such as those involving the Rho proteins.
Rho, the Master Regulators
The small GTPases of the Rho family proteins, such as RhoA, Cdc42, and Rac1, are the master regulators in establishing cell polarity by acting on all three cytoskeletal components. For example, Cdc42 not only directs actin reorganization at the leading edge but also reorganizes intermediate filaments by regulating their transport on the microtubules. The microtubules also direct the transport of various proteins and vesicles, which, in turn, regulate actin dynamics at the leading edge. Such positive feedback helps maintain the synchronized polarity of the different cytoskeletal components.
Suggested Reading
- Seetharaman, Shailaja, and Sandrine Etienne-Manneville. "Cytoskeletal crosstalk in cell migration." Trends in Cell Biology 30.9 (2020): 720-735.Link
- Tang, Dale D., and Brennan D. Gerlach. "The roles and regulation of the actin cytoskeleton, intermediate filaments and microtubules in smooth muscle cell migration." Respiratory research 18.1 (2017): 1-12. Link