Research ArticleDevelopmental Neurobiology

Distinct Cytoplasmic Domains in Plexin-A4 Mediate Diverse Responses to Semaphorin 3A in Developing Mammalian Neurons

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Science Signaling  11 Mar 2014:
Vol. 7, Issue 316, pp. ra24
DOI: 10.1126/scisignal.2004734

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Receptor Domains for Neuronal Retraction or Branching

Various extracellular cues guide neuronal migration and circuit formation. Semaphorin 3A signaling through its receptor Plexin-A4 can elicit either growth cone collapse in the axons of developing sensory neurons or growth and branching in the dendrites of cortical neurons. By expressing various Plexin-A4 mutant proteins in neuronal cultures from Plexin-A4–deficient mice, Mlechkovich et al. identified specific cytoplasmic domains of the receptor responsible for these distinct responses. Although the guanine nucleotide exchange factor FARP2 was involved in both responses, axonal collapse was less dependent on the intracellular FARP2-binding motif in Plexin-A4 than was dendritic growth and branching. Additionally, axon growth cone collapse required a different combination of Plexin-A4 cytoplasmic domains than were required for dendritic arborization. Although the downstream mechanism requires further investigation, the findings show how the composition of receptor cytoplasmic domains can generate different cellular responses to the same ligand. Thus, multiple parallel, intracellular signaling pathways may mediate semaphorin 3A–induced functions, but the responses are first diversified by the Plexin-A4 receptor.

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