Analysis of the Drosophila betaPS subunit indicates that regulation of integrin activity is a primal function of the C8-C9 loop.
Integrin-ligand interactions can be influenced by the sequence in a disulfide-bridged loop between the 8th and 9th beta subunit cysteines. Previous experiments are consistent with C8-C9 loop residues being involved in direct ligand-integrin interactions and/or being important in heterodimer regulation. In betaPS from Drosophila melanogaster and three other dipterans, the C8-C9 loop consists of only two amino acids, and exists in two forms that arise by differential splicing of exon 4. In these species, the betaPS4A isoform has an acidic residue in the first loop position (C8+1), with an alanine or proline in the corresponding position of betaPS4B. Mutations in both isoforms (in combination with alphaPS2) can reduce cell spreading during normal growth, but function is generally restored under conditions that enhance integrin activation. Replacement of the betaPS4A acidic residue with a basic lysine has relatively modest effects on integrin function. Spread cells bearing C8-C9 mutations tend to become less elongated, with reduced frequencies of actin stress fibers. The results indicate that even a minimal, two-residue C8-C9 loop contains structural information that can differentially regulate integrin activity and/or integrin signaling, and that this regulation does not rely on direct molecular interactions involving the variable C8+1 side chains.
Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ 85721 USA. tbunch@u.arizona.edu
Thomas A
TA
Bunch
Steven W
SW
Miller
Danny L
DL
Brower
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion; D002460:Cell Line; D004330:Drosophila / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D039001:Integrin alpha Chains; D016023:Integrins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018402:Manduca / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D029721:Drosophila Proteins; D039001:Integrin alpha Chains; D016023:Integrins; D021122:Protein Subunits; C082188:if protein, Drosophila