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Related Experiment Videos

Modulation of integrin activity is vital for morphogenesis

M D Martin-Bermudo1, O M Dunin-Borkowski, N H Brown

  • 1Wellcome/CRC Institute, Cambridge CB2 1QR, England; and Department of Biochemistry, Cambridge University, Cambridge CB2 1QW, England.

The Journal of Cell Biology
|June 20, 1998
PubMed
Summary

The alpha subunit cytoplasmic domain is crucial for regulating cell adhesion during embryonic development. Disrupting this domain leads to excessive integrin activity, causing abnormal muscle attachments and embryonic lethality.

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Area of Science:

  • Developmental Biology
  • Cell Adhesion
  • Molecular Biology

Background:

  • Cell adhesion is critical for tissue development and is regulated by integrin receptors.
  • Integrin affinity can be modulated by inside-out signaling pathways affecting cytoplasmic domains.
  • Previous studies demonstrated integrin regulation in platelets, lymphocytes, and keratinocytes.

Purpose of the Study:

  • To investigate the role of the alpha subunit cytoplasmic domain in regulating integrin adhesion during embryonic morphogenesis.
  • To determine if the alphaPS2 cytoplasmic domain is essential for controlling integrin activity in specific tissues.

Main Methods:

  • Utilizing mutant forms of the alphaPS2 integrin subunit with deletions in the cytoplasmic domain.
  • Observing the effects of these mutations on PS2 integrin adhesion and muscle attachment patterns in embryos.

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  • Comparing the phenotype in different embryonic tissues, including muscle termini and visceral mesoderm.

    • Main Results:

    • Mutant alphaPS2 integrins with cytoplasmic domain deletions showed excessive activity, leading to aberrant muscle attachments.
    • These defects disrupted normal muscle patterning and resulted in embryonic lethality.
    • Tissue-specific regulation was observed, as a gain-of-function phenotype was not present in the visceral mesoderm.

    Conclusions:

    • The alphaPS2 subunit cytoplasmic domain is essential for the inside-out regulation of integrin affinity during embryonic development.
    • This regulation is critical for precise control of cell adhesion at specific times and locations.
    • Integrin activity regulation is context-dependent and varies across different embryonic tissues.