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Molecular analysis of scabrous mutant alleles from Drosophila melanogaster indicates a secreted protein with two
1Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Abstract:
Mutations at the scabrous locus (sca) affect cell-cell signaling during neural development. Twenty-one mutant alleles of scabrous have been analyzed. Many synthesize no sca protein. In others, a defective protein is arrested intracellularly. Two mutants in which protein is not arrested must affect sca protein function outside the cell. Both affect the fibrinogen related domain (FReD), a 200-amino acid segment conserved in fibrinogen, tenascins, and other proteins. In fibrinogen, this region is involved in protein interactions and is altered in human mutations affecting blood clotting. In sca(UM2), an invariant Asp residue is replaced by Asn. In sca(MSKF) allele has dominant negative properties, indicating that the truncated amino-terminal portion interferes with the function of so me other gene product. These mutations show that the conserved FReD is essential for wild-type sca function, but suggest that the amino-terminal domain also interacts with other proteins, but other neural mutations were without effect. Models for the role of a two-domain protein in neural development are discussed.
Insights
Mutations in the scabrous gene impact neural development by disrupting cell-cell signaling. Key findings highlight the essential role of the fibrinogen-related domain in scabrous protein function.
Area of Science:
- Developmental biology
- Neuroscience
- Molecular genetics
Background:
- The scabrous (sca) locus is crucial for cell-cell signaling during neural development.
- Understanding the molecular mechanisms of sca function is vital for comprehending neural patterning.
Purpose of the Study:
- To analyze the functional impact of various scabrous (sca) mutant alleles.
- To investigate the role of specific protein domains in sca function.
- To elucidate the molecular basis of cell-cell signaling defects in neural development.
Main Methods:
- Analysis of 21 mutant alleles of the scabrous gene.
- Biochemical assessment of sca protein synthesis and intracellular localization.
- Characterization of mutations affecting the fibrinogen-related domain (FReD) and amino-terminal domain.
Main Results:
- Many sca mutants synthesize no functional protein; others show intracellular protein arrest.
- Two mutants, sca(UM2) and sca(MSKF), with altered FReD and amino-terminal domains, respectively, indicate extracellular functions.
- The conserved FReD is essential for wild-type sca function, and the amino-terminal domain mediates interactions with other proteins.
Conclusions:
- The fibrinogen-related domain (FReD) is critical for scabrous protein's role in neural development.
- The amino-terminal domain of scabrous protein interacts with other gene products, influencing cell-cell signaling.
- These findings provide insights into the molecular basis of neural development and cell communication.