Getting neural circuits into shape with semaphorins

Abstract

Semaphorins are key players in the control of neural circuit development. Recent studies have uncovered several exciting and novel aspects of neuronal semaphorin signalling in various cellular processes--including neuronal polarization, topographical mapping and axon sorting--that are crucial for the assembly of functional neuronal connections. This progress is important for further understanding the many neuronal and non-neuronal functions of semaphorins and for gaining insight into their emerging roles in the perturbed neural connectivity that is observed in some diseases. This Review discusses recent advances in semaphorin research, focusing on novel aspects of neuronal semaphorin receptor regulation and previously unexplored cellular functions of semaphorins in the nervous system.

ADAM metalloproteases promote a developmental switch in responsiveness to the axonal repellant Sema3A

“…The Semaphorin family of guidance cues comprises 27 members across eight subclasses, of which the most studied is the class 3 family of secreted Semaphorins 24 . The receptor complex for the axonal repellant Semaphorin3A (Sema3A) comprises two core elements: Neuropilin-1 (Nrp1), which binds the ligand but lacks signalling capabilities [25][26][27] , and type-A Plexin, which transmits the signal 28,29 .…”

Contact-dependent Signaling

“…Some are bound to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor, such as A-ephrins, 43 bone marrow stromal cell antigen 1 (BST1), 40 and semaphorin 7. 30 Interleukin 1 may also be anchored to the extracellular side of the plasma membrane by a lectin or a mannose receptor. Colony-stimulating factor (CsF-1) 26…”

“…Ligands acting as receptors include ephrins, 45 macrophage colony-stimulating factor (M-CSF), 46 BST1, 40,47 Notch ligands, 48 IL15, 24 neuregulins, 49 semaphorins, 30,50 and members of the TNF superfamily.…”

“…(Fig. 1) semaphorins were originally discovered as repulsive axon guidance molecules, 30 but were subsequently found to have significant roles in many other tissues and to play a role in cancer progression. 50 Semaphorins operate either as transmembrane proteins (SEMA1, SEMA4, SEMA5, and SEMA6 members), GPI-anchored proteins (SEMA7A), or as secreted molecules (SEMA2 and SEMA3 members).…”

“…30). Furthermore, SEMA5 signaling is differentially modulated by heparan sulfate proteoglycans (HSPGs) and chondroitin sulfate proteoglycans (CSGPs).…”