The orthologous human and murine semaphorin 6A-1 proteins (SEMA6A-1/Sema6A-1) bind to the enabled/vasodilator-stimulated phosphoprotein-like protein (EVL) via a novel carboxyl-terminal zyxin-like domain.
Neuronal development and apoptosis critically depend on the transformation of extracellular signals to intracellular actions resulting in cytoskeletal rearrangements. Ena/VASP (enabled/vasodilator-stimulated phosphoprotein) proteins play an important role in actin and filament dynamics, whereas members of the semaphorin protein family are guidance signals in embryo- and organogenesis. Here, we report the identification of two novel transmembranous human and murine semaphorins, (HSA)SEMA6A-1 and (MMU)Sema6A-1. These semaphorin 6 variants directly link the Ena/VASP and the semaphorin protein family, since SEMA6A-1/Sema6A-1 is capable of a selective binding to the protein EVL (Ena/VASP-like protein). EVL is the third member of the Ena/VASP family of proteins that was identified sharing the same structural features as Mena (mammalian enabled) and VASP, although its functionality seems to be different from that of the other members. Here we demonstrate that SEMA6A-1/Sema6A-1 is colocalized with EVL via its zyxin-like carboxyl-terminal domain that contains a modified binding motif, which further stresses the existence of functional differences between EVL and Mena/VASP. In addition these findings suggest a completely new role for transmembranous semaphorins such as SEMA6A-1/Sema6A-1 in retrograde signaling.
Klostermann
A
A
MPI of Psychiatry, Independent Research Group Neurodegeneration, Kraepelinstrasse 2, 80804 Munich, Germany.
Lutz
B
B
Gertler
F
F
Behl
C
C
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D015152:Blotting, Northern; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008667:Metalloproteins / Q000737:chemistry; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D011233:Precipitin Tests; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D039961:Semaphorins; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D014162:Transfection; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D003598:Cytoskeletal Proteins; D006023:Glycoproteins; D008667:Metalloproteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C504201:SEMA6A protein, human; C504203:Sema6a protein, mouse; D039961:Semaphorins; C092842:ZYX protein, human; C498285:Zyx protein, mouse; D060589:Zyxin; D000098662:Vasodilator-Stimulated Phosphoprotein