Neurexin III alpha: extensive alternative splicing generates membrane-bound and soluble forms.
The structure of neurexin III alpha was elucidated from overlapping cDNA clones. Neurexin III alpha is highly homologous to neurexins I alpha and II alpha and shares with them a distinctive domain structure that resembles a cell surface receptor. cDNA cloning and PCR experiments revealed alternative splicing at four positions in the mRNA for neurexin III alpha. Alternative splicing was previously observed at the same positions in either neurexin I alpha or neurexin II alpha or both, suggesting that the three neurexins are subject to extensive alternative splicing. This results in hundreds of different neurexins with variations in small sequences at similar positions in the proteins. The most extensive alternative splicing of neurexin III alpha was detected at its C-terminal site, which exhibits a minimum of 12 variants. Some of the alternatively spliced sequences at this position contain in-frame stop codons, suggesting the synthesis of secreted proteins. None of the sequences of the other splice sites in this or the other two neurexins include stop codons. RNA blot analysis demonstrate that neurexin III alpha is expressed in a brain-specific pattern. Our results suggest that the neurexins constitute a large family of polymorphic cell surface proteins that includes secreted variants, indicating a possible role as signaling molecules.
Ushkaryov
Y A
YA
Howard Hughes Medical Institute, University of Texas Southwestern Medical School, Dallas 75235.
Südhof
T C
TC
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D014644:Genetic Variation; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012995:Solubility; D014018:Tissue Distribution
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C082354:neurexin IIIalpha