Disease relevance of SEMA3A

• Introduction of anti-CRMP-62 antibodies into dorsal root ganglion neurons blocks collapsin-induced growth cone collapse [1].
• Perturbation experiments using pertussis toxin (PTX) showed that membrane-induced collapse is mediated via G(o/i) proteins, as is the case for semaphorin/collapsin-1-induced collapse [2].

High impact information on SEMA3A

• Since it induces the collapse and paralysis of neuronal growth cones in vitro, we have named it collapsin [3].
• Recombinant collapsin causes sensory ganglion growth cones to collapse but not retinal ganglion cell growth cones [3].
• Here we use a Xenopus laevis oocyte expression system to identify molecules involved in collapsin signalling, because several experiments have raised the possibility that heterotrimeric GTP-binding proteins might participate in these events [1].
• Two other secreted members of the semaphorin family, collapsin-2 and -3, are structurally similar to collapsin-1 but have different biological activities [4].
• We have completed the cloning of chick collapsin-3 and -5 and show that collapsin-1, -2, -3, and -5 bind to overlapping but distinct axon tracts [5].

Biological context of SEMA3A

• One is structurally very similar to collapsin but is only 50% identical in its amino acid sequence [6].
• These results suggest that collapsin-1 signalling can contribute to the patterning of neural crest cell migration in the developing chick [7].
• Because growth cone collapse is associated with actin depolymerization, we considered whether small GTP-binding proteins of the rho subfamily might participate in collapsin-1 signal transduction [8].
• Collapsin-1 covalently dimerizes, and dimerization is necessary for collapse activity [9].
• Structural features of collapsin required for biological activity and distribution of binding sites in the developing chick [10].

Anatomical context of SEMA3A

• The collapsin-related genes exhibit distinct but overlapping patterns of mRNA expression in the developing spinal cord and the developing visual system [6].
• In explant cultures of spinal cord segments with attached sensory ganglia, the spatial extent of SEMA3A expression varied in different explants, but in each case the growth of trkA(+) sensory collaterals was largely excluded from areas of SEMA3A expression [11].
• The N-terminal half of collapsin shares significant homology with fasciclin IV, a growth cone guidance protein in grasshopper [3].
• Specific mutants of small GTPases were capable of desensitizing growth cones to CNS myelin or collapsin-1 [12].
• Evidence for collapsin-1 functioning in the control of neural crest migration in both trunk and hindbrain regions [7].

Associations of SEMA3A with chemical compounds

• A chick brain glycoprotein, collapsin, has been shown to be a good candidate for a repulsive guidance cue [6].
• C3 transferase-treated growth cones exhibit little or no lamellipodial spreading and are minimally responsive to collapsin-1 and myelin [8].
• Here we report the distribution of collapsin-1 message as demonstrated by in situ hybridization using digoxigenin-labeled RNA probes in wholemounts and tissue sections [13].

Other interactions of SEMA3A

• Consistent with the insensitivity of trkC(+) collaterals to SEMA3A, these collaterals did not express neuropilin-1, a receptor for SEMA3A [11].
• Conversely, growth cones chronically cultured in NGF rapidly increase their sensitivity to collapsin-1 with acute exposure to BDNF [14].
• In order to test the function of collapsin-1 on the migration of neural crest cells, an in vitro assay was used in which collapsin-1-Fc was immobilised in alternating stripes consisting of collapsin-Fc/fibronectin versus fibronectin alone [7].

References