Cellugyrin, a novel ubiquitous form of synaptogyrin that is phosphorylated by pp60c-src.
Synaptogyrin is an abundant membrane protein of synaptic vesicles containing four transmembrane regions and a C-terminal cytoplasmic tail that is tyrosine phosphorylated. We have now identified a novel isoform of synaptogyrin called cellugyrin that exhibits 47% sequence identity with synaptogyrin. In rat tissues, cellugyrin and synaptogyrins are expressed in mirror image patterns. Cellugyrin is ubiquitously present in all tissues tested with the lowest levels in brain tissue, whereas synaptogyrin protein is only detectable in brain. Transfection studies in COS cells demonstrated that both cellugyrin and synaptogyrin are tyrosine phosphorylated in vivo by pp60c-src, and experiments with recombinant proteins showed that pp60c-src phosphorylates the cytoplasmic tails of these proteins in vitro. Cellugyrin and synaptogyrin co-localize when transfected into COS cells but are differentially distributed in brain, the only tissue where both proteins are detectable. Our data suggest that the synaptic vesicle protein synaptogyrin is a specialized version of a ubiquitous protein, cellugyrin, with the two proteins sharing structural similarity but differing in localization. This finding supports the emerging concept of synaptic vesicles as the simplified and specialized form of a generic trafficking organelle. The conserved tyrosine phosphorylation of cellugyrin and synaptogyrins suggests a link between tyrosine phosphorylation via pp60c-src and membrane traffic.
Janz
R
R
Department of Molecular Genetics and Howard Hughes Medical Institute, The University of Texas Southwestern Medical Center, Dallas, Texas 75235, USA.
Südhof
T C
TC
D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002451:Cell Compartmentation; D003001:Cloning, Molecular; D005089:Exocytosis; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism*; D051381:Rats; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D062805:Synaptogyrins; D016708:Synaptophysin / Q000031:analogs & derivatives; D014018:Tissue Distribution
D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C504260:SYNPR protein, human; D062805:Synaptogyrins; D016708:Synaptophysin; C504262:Synpr protein, rat; C504590:Sypl1 protein, rat; D016392:Proto-Oncogene Proteins pp60(c-src)