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PMID:19788569

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Citation

Vodrazka, P, Korostylev, A, Hirschberg, A, Swiercz, JM, Worzfeld, T, Deng, S, Fazzari, P, Tamagnone, L, Offermanns, S and Kuner, R (2009) The semaphorin 4D-plexin-B signalling complex regulates dendritic and axonal complexity in developing neurons via diverse pathways. Eur. J. Neurosci. 30:1193-208

Abstract

Semaphorins and their receptors, plexins, have emerged as key regulators of various aspects of neuronal development. In contrast to the Plexin-A family, the cellular functions of Plexin-B family proteins in developing neurons are only poorly understood. An activation of Plexin-B1 via its ligand, semaphorin 4D (Sema4D), produces an acute collapse of axonal growth cones in hippocampal and retinal neurons over the early stages of neurite outgrowth. However, the functional role of Sema4D-Plexin-B interactions over subsequent stages of neurite development, differentiation and maturation has not been characterized. Here we addressed this question using morphogenetic assays and time-lapse imaging on developing rat hippocampal neurons as a model system. Interestingly, Sema4D treatment over several hours was observed to promote branching and complexity in hippocampal neurons via the activation of Plexin-B1. The activation of receptor tyrosine kinases and the Rho kinase following Sema4D treatment was found to control dendritic and axonal morphogenesis by differentially regulating branching and extension. Phosphoinositide-3-kinase, but not extracellular signal-regulated kinase 1/2, was observed to be important for the stimulatory effects of Sema4D on dendritic branching. Furthermore, we observed that the mammalian target of rapamycin is activated downstream of Plexin-B1 and contributes to Sema4D-induced effects on dendritic branching. In contrast, glycogen synthase kinase-3 beta, another effector of phosphoinositide-3-kinase signalling, was not involved. Thus, our results show that Sema4D-Plexin-B interactions modulate dendritic and axonal arborizations of developing neurons by co-ordinated and concerted activation of diverse signalling pathways.

Links

PubMed Online version:10.1111/j.1460-9568.2009.06934.x

Keywords

Animals; Antigens, CD/metabolism; Axons/physiology; Cells, Cultured; Dendrites/physiology; GTPase-Activating Proteins/metabolism; Hippocampus/cytology; Hippocampus/growth & development; Hippocampus/physiology; Mice; Mice, Knockout; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Neurons/physiology; Phosphatidylinositol 3-Kinases/metabolism; Rats; Rats, Sprague-Dawley; Receptor Protein-Tyrosine Kinases/metabolism; Receptors, Cell Surface/genetics; Receptors, Cell Surface/metabolism; Semaphorins/metabolism; Signal Transduction

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:PLXB1

involved_in

GO:0008360: regulation of cell shape

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PLXB1

involved_in

GO:0014068: positive regulation of phosphatidylinositol 3-kinase signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PLXB1

enables

GO:0017154: semaphorin receptor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:PLXB1

involved_in

GO:0048812: neuron projection morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PLXB1

involved_in

GO:0071526: semaphorin-plexin signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:PLXB1

involved_in

GO:0043547: positive regulation of GTPase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SEM4D

involved_in

GO:0048814: regulation of dendrite morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SEM4D

involved_in

GO:0048672: positive regulation of collateral sprouting

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SEM4D

involved_in

GO:0071526: semaphorin-plexin signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SEM4D

involved_in

GO:0043547: positive regulation of GTPase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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