Plexin

Extracellular All plexins have an extracellular SEMA domain at their N-terminus. This is followed by alternating plexin, semaphorin, and integrin (PSI) domains and immunoglobulin-like, plexin, and transcription factors (IPT) domains. Each of these is named for the proteins in which their structure is conserved. Collectively, the extracellular region resembles a curved stalk projecting in a clockwise direction. This allows for co-localization of plexin dimers to be primed for binding of semaphorin dimers and activation of intracellular machinery. These GTPases can have a number of downstream effects, but in particular to Plexin expressed on axonal growth cones, the concentration the secondary messenger cyclic guanosine monophosphate (cGMP) increases within the cell. The structure of the Class B plexins has an additional extracellular site for cleavage by convertases, enzymes which modify plexin precursor polypeptides into their final peptide sequence, as well as a structural PDZ interaction motif on its C-terminus. C-class plexins have fewer structural Methionine-Related Sequences (MRS) and IPT domains. D-class plexins have an additional modification in one of the MRS domains == Function ==

Plexin receptors largely act to signal the binding of semaphorin signaling proteins in a short-distance inhibitory manner. Each class of plexin has a range of specificity, meaning they could bind specifically to one or more semaphorin isomers. Plexins also have varying effects on development depending on their expression in different tissue types. Plexin receptors have implications in neural development and axon growth guidance, angiogenesis and heart development, skeletal and kidney morphogenesis, and in the immune system. Genetic knockout of plexins have shown to be lethal at embryonic stages due to severe developmental defects in body systems regulated by semaphorin-plexin signaling. Axon guidance • Plexin receptors on axon growth cones receive local semaphorin signaling and impede growth in that direction. Angiogenesis and heart development • PLXND1 is involved in guiding the growth of new blood vessels. Cells expressing Sema3E do not need additional vascularization. Developing vessels will have their growth towards these cells inhibited upon PLXND1 binding to Sema3E independent of Neuropilin. • PLXNA2 and PLXND1 modulate proper development of cardiac structures. == References ==