Dcas supports cell polarization and cell-cell adhesion complexes in development

Nadezhda Tikhmyanova1, Alexei V Tulin, Fabrice Roegiers

  • 1Fox Chase Cancer Center, Philadelphia, Pennsylvania, United States of America.

Plos One
|September 3, 2010
PubMed

Insights

Deleting the Drosophila Cas gene, Dcas, revealed its crucial role in cell adhesion signaling during development. Loss of Dcas significantly impacts cell polarity and modifies phenotypes in mutations affecting integrins and E-cadherin.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Genetics

Background:

  • Mammalian Cas proteins are key regulators of cell migration, division, and survival, with deregulation implicated in cancer.
  • The presence of four paralogous Cas family members in mammals complicates developmental studies.
  • The single Drosophila Cas gene, Dcas, offers a model to investigate Cas protein function in development.

Purpose of the Study:

  • To investigate the developmental function of the Drosophila Cas gene, Dcas.
  • To determine the role of Dcas in modulating phenotypes associated with mutations in integrins and cell adhesion pathways.

Main Methods:

  • Gene deletion of the single Drosophila Cas gene (Dcas).
  • Genetic analysis of Dcas in combination with mutations affecting integrins (If, mew), focal adhesion kinase (Fak56D), Src kinase (Src42A), and E-cadherin (Shg) and its associated proteins (p120-catenin, beta-catenin).
  • Phenotypic analysis of embryonic development, focusing on cell polarity and protein expression.

Main Results:

  • Loss of Dcas alone had minimal impact on embryonic development.
  • Dcas deficiency significantly modulated the severity of developmental phenotypes in mutants affecting integrins and their downstream effectors.
  • Fak56D-Dcas double mutants exhibited severe cell polarity defects, including E-cadherin mislocalization and reduced expression.
  • Loss of Dcas modified embryonic lethal phenotypes associated with mutations in E-cadherin and its signaling partners.

Conclusions:

  • Cas proteins play a significant role in cell-cell adhesion signaling during development.
  • Dcas functions as a critical modulator of developmental pathways involving cell adhesion and polarity.
  • The study highlights the conserved function of Cas proteins in regulating developmental processes.

Related Concept Videos

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,...
Cell Adhesion in Plants01:14

Cell Adhesion in Plants

Plants have rigid cell walls that are made up of cell wall polysaccharides that mediate cell-cell adhesion. The primary cell walls of plants consist of two independent and interacting polysaccharide networks: a pectin matrix that embeds the second network comprising cellulose and hemicelluloses.
Pectins are complex heteropolymers mainly composed of negatively-charged α-D-glucopyranosyl uronic acid and some neutral glycosyl residues such as α-L-rhamnopyranose, α-L-arabinofuranose, and...
Cell Adhesion Molecules - Types and Functions01:20

Cell Adhesion Molecules - Types and Functions

Cell adhesion molecules (CAMs) are pivotal to multicellularity and the coordinated functioning of tissues and organ systems. They enable physical interactions between cells and provide mechanical strength to tissues. They also function as receptors for signal transmission across the plasma membrane. The CAMs are broadly classified into four families - integrins, cadherins, selectins, and immunoglobulin-like CAMs (IgCAMs).
CAM Families
The Integrin family of proteins is primarily  involved in a...
Cell Adhesion Molecules - Types and Functions01:20

Cell Adhesion Molecules - Types and Functions

Cell adhesion molecules (CAMs) are pivotal to multicellularity and the coordinated functioning of tissues and organ systems. They enable physical interactions between cells and provide mechanical strength to tissues. They also function as receptors for signal transmission across the plasma membrane. The CAMs are broadly classified into four families - integrins, cadherins, selectins, and immunoglobulin-like CAMs (IgCAMs).
CAM Families
The Integrin family of proteins is primarily  involved in a...
Immunoglobulin-like Cell Adhesion Molecules01:31

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...
Cadherins in Tissue Organization01:19

Cadherins in Tissue Organization

The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...