TY - JOUR
T1 - 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 - Mejias-Estevez, Rebeca M
AU - Hand, Randal
AU - Wang, Tao
AU - Ginty, David D.
AU - Kolodkin, Alex L.
N1 - Funding Information:
We thank Dontais Johnson and Sarah Mitchell for excellent technical assistance. We also thank Martin M Riccomagno and other Kolodkin laboratory members for discussions. We thank Dr Joseph A Gogos for providing the Zdhhc8-/- mouse line and Dr Masaki Fukata for providing DHHC expression plasmids. This work was supported by NIH grant MH100024-Project #3 (ALK); previous support from the Howard Hughes Medical Institute (ALK); NIH grant R21NS085358 (EM, TW): and the State Scholarships Foundation (EK) and the AG Leventis Foundation (EK). DDG is an Investigator of the Howard Hughes Medical Institute.
Funding Information:
This work was supported by NIH grant MH100024-Project #3 (ALK); previous support from the Howard Hughes Medical Institute (ALK); NIH grant R21NS085358 (EM, TW): and the State Scholar-ships Foundation (EK) and the AG Leventis Foundation (EK). DDG is an Investigator of the Howard Hughes Medical Institute.
Publisher Copyright:
© Koropouli et al.
PY - 2023/4
Y1 - 2023/4
N2 - 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 neuropi-lin-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, palmi-toyl acyltransferase-substrate specificity is essential for establishing compartmentalized neuronal structure and functional responses to extrinsic guidance cues.
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 neuropi-lin-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, palmi-toyl acyltransferase-substrate specificity is essential for establishing compartmentalized neuronal structure and functional responses to extrinsic guidance cues.
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U2 - 10.7554/eLife.83217
DO - 10.7554/eLife.83217
M3 - Article
C2 - 37010951
AN - SCOPUS:85151806963
SN - 2050-084X
VL - 12
JO - eLife
JF - eLife
M1 - e83217
ER -