Complexes of plexin-A4 and plexin-D1 convey semaphorin-3C signals to induce cytoskeletal collapse in the absence of neuropilins

• DOI: 10.1242/jcs.208298
• Publication Date: 2018-04-16T10:25:14Z
• Authors: Tatyana Smolkin; Inbal Nir-Zvi; Nerri Duvshani; Yelena Mumblat; Ofra Kessler; Gera Neufeld
• Keywords: 0303 health sciences; Membrane Glycoproteins; Cell Adhesion Molecules, Neuronal; Intracellular Signaling Peptides and Proteins; Receptors, Cell Surface; Semaphorins; 03 medical and health sciences; Cell Line, Tumor; Humans; Neuropilins; Glioblastoma; Cytoskeleton; Signal Transduction

ABSTRACT Class-3 semaphorin guidance factors bind to receptor complexes containing neuropilin and plexin receptors. A semaphorin may bind to several receptor complexes containing somewhat different constituents, resulting in diverse effects on cell migration. U87MG glioblastoma cells express both neuropilins and the four class-A plexins. Here, we show that these cells respond to Sema3A or Sema3B by cytoskeletal collapse and cell contraction but fail to contract in response to Sema3C, Sema3D, Sema3G or Sema3E, even when class-A plexins are overexpressed in the cells. In contrast, expression of recombinant plexin-D1 enabled contraction in response to these semaphorins. Surprisingly, unlike Sema3D and Sema3G, Sema3C also induced the contraction and repulsion of plexin-D1-expressing U87MG cells in which both neuropilins were knocked out using CRISPR/Cas9. In the absence of neuropilins, the EC50 of Sema3C was 5.5 times higher, indicating that the neuropilins function as enhancers of plexin-D1-mediated Sema3C signaling but are not absolutely required for Sema3C signal transduction. Interestingly, in the absence of neuropilins, plexin-A4 formed complexes with plexin-D1, and was required in addition to plexin-D1 to enable Sema3C-induced signal transduction.