Palmitoylation regulates neuropilin-2 localization and function in cortical neurons and conveys specificity to semaphorin signaling via palmitoyl acyltransferases

Author:

Koropouli Eleftheria1ORCID,Wang Qiang1,Mejías Rebeca2ORCID,Hand Randal1,Wang Tao3,Ginty David D4ORCID,Kolodkin Alex L1ORCID

Affiliation:

1. The Solomon H Snyder Department of Neuroscience, Johns Hopkins University School of Medicine

2. Department of Physiology,University of Seville

3. McKusick-Nathans Institute of Genetic Medicine and Department of Pediatrics, The Johns Hopkins University School of Medicine

4. Department of Neurobiology, Howard Hughes Medical Institute, Harvard Medical School

Abstract

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.

Funder

National Institutes of Health

State Scholarships Foundation

A.G. Leventis Foundation

Howard Hughes Medical Institute

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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