| First Author | Merte J | Year | 2010 |
| Journal | J Neurosci | Volume | 30 |
| Issue | 16 | Pages | 5767-75 |
| PubMed ID | 20410128 | Mgi Jnum | J:159834 |
| Mgi Id | MGI:4452536 | Doi | 10.1523/JNEUROSCI.5061-09.2010 |
| Citation | Merte J, et al. (2010) A forward genetic screen in mice identifies Sema3A(K108N), which binds to neuropilin-1 but cannot signal. J Neurosci 30(16):5767-75 |
| abstractText | We have performed a three-generation, forward genetic screen to identify recessive mutations that affect the patterning of the peripheral nervous system. Using this assay, we identified Sema3A(K108N), a novel loss-of-function allele of Sema3A. Class 3 semaphorins, which include Sema3A, are structurally conserved secreted proteins that play critical roles in the development and function of the nervous system. Sema3A(K108N) mutant mice phenocopy Sema3A-null mice, and Sema3A(K108N) protein fails to repel or collapse DRG axons in vitro. K108 is conserved among semaphorins, yet the loss-of-function effects associated with K108N are not the result of impaired expression, secretion, or binding of Sema3A to its high-affinity receptor Neuropilin-1 (Npn-1). Using in silico modeling and mutagenesis of other semaphorin family members, we predict that Sema3A(K108N) interacts poorly with the Npn-1/PlexA holoreceptor and, thus, interferes with its ability to signal at the growth cone. Therefore, through the use of a forward-genetic screen we have identified a novel allele of Sema3A that provides structural insight into the mechanism of Sema3A/Npn-1/PlexinA signaling. |
