Redundant functions but temporal and regional regulation of two alternatively spliced isoforms of semaphorin 3F in the nervous system.
SEMA3F is a secreted semaphorin that affects axon and cell guidance in the developing nervous system, and is also thought to have anti-tumor activity. Two spliced forms of SEMA3F have been identified that differ by the insertion of 31 amino acids in the sema domain. Here, we investigated the bioactivity of these isoforms and show, using coculture and binding assays, that they share common axonal chemorepulsive properties and binding to neuropilin receptors. SEMA3F isoforms were also found to regulate endothelial cell morphology by remodeling lamellipodial protrusions. Although Sema3F expression globally decreased during mouse development, we noted an enrichment of the longest isoform at postnatal stages in some territories such as the brainstem and spinal cord. These results indicate that although functionally redundant in cell culture assays, Sema3F spliced forms are characterized in vivo by a temporal and regional specific regulation during maturation of the nervous system.
Laboratoire de Génétique Humaine, IBMIG, EA 2224, Université de Poitiers, 40, Av. du recteur Pineau, 86022 Poitiers cedex, France.
Sophie
S
Kusy
Lydiane
L
Funkelstein
David
D
Bourgais
Harry
H
Drabkin
Geneviève
G
Rougon
Joëlle
J
Roche
Valérie
V
Castellani
D017398:Alternative Splicing; D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002522:Chlorocebus aethiops; D005786:Gene Expression Regulation / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009420:Nervous System / Q000254:growth & development / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D013997:Time Factors
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; C491229:Sema3f protein, mouse