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Molecular mechanisms of human melanocyte attachment to fibronectin
G Scott1, D H Ryan, J B McCarthy
1Department of Dermatology, University of Rochester Medical School, NY 14607.
Abstract:
In this report we show that fetal and neonatal melanocyte attachment to fibronectin (FN) is inhibited by antibodies to the beta 1 integrin subunit, suggesting a role for these molecules in melanocyte attachment to FN. The VLA-5 integrin was shown to be the predominant receptor for fetal melanocyte attachment to FN, in contrast with neonatal melanocytes in which the very late antigen (VLA)-5, VLA-3, and alpha v integrins each contributed to melanocyte attachment to FN. Peptides containing the arginyl-glycyl-aspartyl-serine (RGDS) sequence inhibited fetal and neonatal melanocyte attachment to FN by a maximum of 48% and 85%, respectively. The almost complete inhibition of neonatal melanocyte attachment to FN by RGDS-containing peptides suggests that the central cell-binding domain of FN is the primary recognition site for neonatal cell attachment to FN. Fetal and neonatal melanocytes showed a concentration-dependent attachment to two proteolytically derived fragments of the FN molecule: a 75-kD fragment, which contains the central cell-binding domain, and 33/66-kD fragments of the FN molecule, which encompass the heparin-binding domains V and VI. Antibodies to the beta 1 subunit inhibited fetal and neonatal melanocyte attachment to the 33/66-kD fragments by a maximum of only 15% and 24%, respectively, suggesting that other, non-integrin, receptors are involved in melanocyte recognition of this portion of the FN molecule. We propose that human fetal and neonatal melanocytes attach to FN by different complements of receptors and ligand target sequences, and that these differences may direct melanocyte interactions with FN during development.
Insights
Fetal and neonatal melanocytes use different receptors to attach to fibronectin (FN). This suggests distinct molecular interactions guide melanocyte development and migration.
Area of Science:
- Cell Biology
- Developmental Biology
- Dermatology
Background:
- Melanocyte attachment to fibronectin (FN) is crucial for development.
- Integrins are key cell surface receptors mediating cell adhesion.
Purpose of the Study:
- To investigate the specific integrin receptors and molecular domains involved in fetal and neonatal melanocyte attachment to fibronectin.
- To understand developmental differences in melanocyte-FN interactions.
Main Methods:
- Antibody inhibition assays targeting beta 1 integrin subunit.
- Use of Very Late Antigen (VLA)-5, VLA-3, and alpha v integrins.
- Peptide inhibition assays using arginyl-glycyl-aspartyl-serine (RGDS) sequence.
- Attachment assays using FN fragments containing cell-binding and heparin-binding domains.
Main Results:
- Fetal melanocyte attachment to FN primarily involves VLA-5 integrin.
- Neonatal melanocyte attachment involves VLA-5, VLA-3, and alpha v integrins.
- RGDS peptides significantly inhibited neonatal (85%) vs. fetal (48%) melanocyte attachment to FN.
- Non-integrin receptors are implicated in neonatal melanocyte attachment to FN heparin-binding domains.
Conclusions:
- Human fetal and neonatal melanocytes utilize distinct receptor repertoires and target sequences for fibronectin binding.
- These differences in receptor usage and ligand recognition likely influence melanocyte behavior during development.