TY - JOUR TI - Palmitoylation regulates neuropilin-2 localization and function in cortical neurons and conveys specificity to semaphorin signaling via palmitoyl acyltransferases AU - Koropouli, Eleftheria AU - Wang, Qiang AU - Mejías, Rebeca AU - Hand, Randal AU - Wang, Tao AU - Ginty, David D AU - Kolodkin, Alex L A2 - Yasuda, Ryohei A2 - Cooper, Jonathan A VL - 12 PY - 2023 DA - 2023/04/03 SP - e83217 C1 - eLife 2023;12:e83217 DO - 10.7554/eLife.83217 UR - https://doi.org/10.7554/eLife.83217 AB - Secreted semaphorin 3F (Sema3F) and semaphorin 3A (Sema3A) exhibit remarkably distinct effects on deep layer excitatory cortical pyramidal neurons; Sema3F mediates dendritic spine pruning, whereas Sema3A promotes the elaboration of basal dendrites. Sema3F and Sema3A signal through distinct holoreceptors that include neuropilin-2 (Nrp2)/plexinA3 (PlexA3) and neuropilin-1 (Nrp1)/PlexA4, respectively. We find that Nrp2 and Nrp1 are S-palmitoylated in cortical neurons and that palmitoylation of select Nrp2 cysteines is required for its proper subcellular localization, cell surface clustering, and also for Sema3F/Nrp2-dependent dendritic spine pruning in cortical neurons, both in vitro and in vivo. Moreover, we show that the palmitoyl acyltransferase ZDHHC15 is required for Nrp2 palmitoylation and Sema3F/Nrp2-dependent dendritic spine pruning, but it is dispensable for Nrp1 palmitoylation and Sema3A/Nrp1-dependent basal dendritic elaboration. Therefore, palmitoyl acyltransferase-substrate specificity is essential for establishing compartmentalized neuronal structure and functional responses to extrinsic guidance cues. KW - neuropilins KW - neuropilin-2 KW - Sema3F KW - palmitoylation KW - palmitoyl acyltransferases KW - cortical neurons JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -