Plexin B3 promotes neurite outgrowth, interacts homophilically, and interacts with Rin.
BACKGROUND
Plexins, known to date as receptors of semaphorins, are implicated in semaphorin-mediated axon repulsion and growth cone collapse. However, subtype-specific functions of the majority of the nine members of the mammalian plexin family are largely unknown. In order to investigate functional properties of B-plexins, we analyzed the expression of human and murine plexin B3 and expressed full-length human plexins B2 (B2) and B3 (B3) in NIH-3T3 cells.


RESULTS
Unexpectedly, B3 strongly and B2 moderately stimulate neurite outgrowth of primary murine cerebellar neurons. Both plexins mediate Ca2+/Mg2+-dependent cell aggregation due to homophilic trans-interaction, which is strong in the case of B3 and moderate for B2. Using different deletion constructs we show that the sema domain of B3 is essential for homophilic interaction. Using yeast two-hybrid analysis, we identified the neuron-specific and calmodulin-binding Ras-related GTPase Rin as an interaction partner of the intracellular part of B3, but not of B2. Rin, also known for its neurite outgrowth-inducing characteristics, co-localizes and co-immunoprecipitates with B3 in co-transfected COS-7 cells.


CONCLUSIONS
Our data suggest an involvement of homophilic interaction of B3 in semaphorin-independent signaling mechanisms positively influencing neuronal morphogenesis or function. Furthermore the neuron-specific small GTPase Rin is involved in downstream signaling of plexin B3.
Hartwig
Christine
C
Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, Universität Hamburg, Hamburg, Germany. hartwig@uke.uni-hamburg.de
Veske
Andres
A
Krejcova
Sarka
S
Rosenberger
Georg
G
Finckh
Ulrich
U
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009414:Nerve Growth Factors / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D016501:Neurites / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D018631:ras Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D019006:Neural Cell Adhesion Molecules; C496426:PLXNB3 protein, human; C401848:Rin protein (GTPase); D018631:ras Proteins