Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid

Aleksandra Czuchra1, Xunwei Wu, Hannelore Meyer

  • 1Heisenberg Group "Regulation of Cytoskeletal Organization," Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.

Insights

Loss of Cdc42 (cell division control protein 42) did not impact filopodia or migration speed but affected cell shape and directionality. Other Rho-family GTPases are crucial for cell polarity during migration.

Area of Science:

  • Cell Biology
  • Cytoskeletal Dynamics
  • Cell Migration

Background:

  • Cdc42 (cell division control protein 42) is a small GTPase regulating cytoskeleton and cell polarity.
  • Its precise role in filopodia formation and directed cell migration requires further elucidation.

Purpose of the Study:

  • To investigate the essential role of Cdc42 in filopodia formation and directed cell migration.
  • To understand Cdc42's contribution to cell polarity maintenance during migration.

Main Methods:

  • Conditional gene inactivation to generate Cdc42-deficient fibroblastoid cells.
  • Analysis of cell morphology, migration speed, directionality, and Golgi reorientation.
  • Expression of dominant-negative Cdc42 in Cdc42-null cells.

Main Results:

  • Cdc42 deficiency did not affect filopodia, lamellipodia formation, migration speed, or mitosis.
  • Cdc42-null cells showed altered shape (elongated, reduced area) and decreased migration directionality.
  • Dominant-negative Cdc42 expression severely impaired directed migration, cell directionality, Golgi polarization, and protrusion directionality.

Conclusions:

  • Cdc42 is not essential for filopodia or lamellipodia formation or basal migration speed.
  • Cdc42 plays a significant role in maintaining cell polarity and directionality during directed migration.
  • Other Rho-family GTPases, potentially sharing Guanine nucleotide exchange factors (GEFs) with Cdc42, are also critical for establishing and maintaining cell polarity in directed migration.

Related Concept Videos

Mechanism of Filopodia Formation01:39

Mechanism of Filopodia Formation

Filopodia are thin, actin-rich cellular protrusions that play an important role in many fundamental cellular functions. They vary in their occurrence, length, and positioning in different cell types, suggesting their diverse roles.
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...
Cell Polarization by Rho Proteins01:21

Cell Polarization by Rho Proteins

Cell polarity is the asymmetric distribution of cellular and membrane components, making one side of the cell different from the other. This polarity is essential to many processes such as embryogenesis, axon migration, glucose transport across epithelial cells, and directional cell migration. A migrating cell responds to intracellular or extracellular signals via molecular cascades that reorganize the actin cytoskeleton to establish this polarity. In these cells, the Rho family proteins Cdc42,...
Cytoskeletal Coordination in Cell Migration01:32

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...
Cell Migration01:09

Cell Migration

Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
Cell Migration01:19

Cell Migration

Cell migration is a process by which the cells move from one location to another, playing an essential role in embryological development, repair and regeneration, immune response, and metastasis. Cells migrate in response to chemical or mechanical signals generated by specific organs or tissues. The overall mechanism includes three steps - polarization, protrusion, and release. Polarization involves the formation of a distinct cell front and rear, which determines the direction of movement.
Adaptability of Cytoskeletal Filaments01:12

Adaptability of Cytoskeletal Filaments

The cytoskeleton is a complex dynamic structure performing varied functions based on cellular requirements. The adaptability of the individual filaments in the cytoskeleton determines their ability to perform various functions within the cell. It can undergo rapid reorganization during processes like cell division or remain stable for several hours as in the interphase. The adaptability of these filaments depends on stringent regulatory mechanisms. The microfilament and microtubules of the...