Plexin A4 (PLXNA4)

Tran et al. (2009) found that a Sema3A-Npn1/PlexA4 signaling cascade controls basal dendritic arborization in layer V cortical neurons, but does not influence spine morphogenesis or distribution. In contrast, they demonstrated that the secreted semaphorin Sema3F is a negative regulator of spine development and synaptic structure. Mice with null mutations in genes encoding Sema3F and its holoreceptor components neuropilin-2 (NPN2) and plexin A3 (PLEXA3) exhibit increased dentate gyrus granule cell and cortical layer V pyramidal neuron spine number and size, and also aberrant spine distribution. Moreover, Sema3F promotes loss of spines and excitatory synapses in dissociated neurons in vitro, and in Npn2-null brain slices cortical layer V and dentate gyrus granule cells exhibit increased miniature excitatory postsynaptic current frequency.