Interplay between phosphorylation and palmitoylation mediates plasma membrane targeting and sorting of GAP43

DC FieldValueLanguage
dc.contributor.authorGauthier-Kemper, Anne
dc.contributor.authorIgaev, Maxim
dc.contributor.authorSuendermann, Frederik
dc.contributor.authorJanning, Dennis
dc.contributor.authorBruehmann, Joerg
dc.contributor.authorMoschner, Katharina
dc.contributor.authorReyher, Hans-Juergen
dc.contributor.authorJunge, Wolfgang
dc.contributor.authorGlebov, Konstantin
dc.contributor.authorWalter, Jochen
dc.contributor.authorBakota, Lidia
dc.contributor.authorBrandt, Roland
dc.date.accessioned2021-12-23T16:11:13Z-
dc.date.available2021-12-23T16:11:13Z-
dc.date.issued2014
dc.identifier.issn10591524
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/9590-
dc.description.abstractPhosphorylation and lipidation provide posttranslational mechanisms that contribute to the distribution of cytosolic proteins in growing nerve cells. The growth-associated protein GAP43 is susceptible to both phosphorylation and S-palmitoylation and is enriched in the tips of extending neurites. However, how phosphorylation and lipidation interplay to mediate sorting of GAP43 is unclear. Using a combination of biochemical, genetic, and imaging approaches, we show that palmitoylation is required for membrane association and that phosphorylation at Ser-41 directs palmitoylated GAP43 to the plasma membrane. Plasma membrane association decreased the diffusion constant fourfold in neuritic shafts. Sorting to the neuritic tip required palmitoylation and active transport and was increased by phosphorylation-mediated plasma membrane interaction. Vesicle tracking revealed transient association of a fraction of GAP43 with exocytic vesicles and motion at a fast axonal transport rate. Simulations confirmed that a combination of diffusion, dynamic plasma membrane interaction and active transport of a small fraction of GAP43 suffices for efficient sorting to growth cones. Our data demonstrate a complex interplay between phosphorylation and lipidation in mediating the localization of GAP43 in neuronal cells. Palmitoylation tags GAP43 for global sorting by piggybacking on exocytic vesicles, whereas phosphorylation locally regulates protein mobility and plasma membrane targeting of palmitoylated GAP43.
dc.description.sponsorshipDeutsche Forschungsgemeinschaft GrantGerman Research Foundation (DFG) [SFB944]; Graduate College 612 of the Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG); state of Lower SaxonyEuropean Commission; We thank Amrei Janicke, Nina Jodden, and Ira Strubing for help with immunofluorescence microscopy and morphometric evaluation, Benedikt Niewidok for help with cloning, and Vanessa Herkenhoff for technical assistance. We also thank Michael Kemper for helpful suggestions on the manuscript. W.J. holds a Niedersachsen-Professur, awarded by the state of Lower Saxony. This work was supported by a fellowship of the Graduate College 612 of the Deutsche Forschungsgemeinschaft (A. G.) and by Deutsche Forschungsgemeinschaft Grant SFB944, Z-project.
dc.language.isoen
dc.publisherAMER SOC CELL BIOLOGY
dc.relation.ispartofMOLECULAR BIOLOGY OF THE CELL
dc.subjectBRAIN
dc.subjectCALMODULIN
dc.subjectCell Biology
dc.subjectCORTICAL-NEURONS
dc.subjectFATTY ACYLATION
dc.subjectGROWTH
dc.subjectIDENTIFICATION
dc.subjectNEUROMODULIN GAP-43
dc.subjectPROTEIN-KINASE-C
dc.subjectSEQUENCE MOTIFS
dc.subjectTRAFFICKING
dc.titleInterplay between phosphorylation and palmitoylation mediates plasma membrane targeting and sorting of GAP43
dc.typejournal article
dc.identifier.doi10.1091/mbc.E13-12-0737
dc.identifier.isiISI:000344236100012
dc.description.volume25
dc.description.issue21
dc.description.startpage3284
dc.description.endpage3299
dc.contributor.orcid0000-0001-8781-1604
dc.contributor.orcid0000-0002-8777-5006
dc.contributor.orcid0000-0002-4678-2912
dc.contributor.orcid0000-0003-0101-1257
dc.contributor.researcheridB-3677-2014
dc.contributor.researcheridH-6108-2018
dc.identifier.eissn19394586
dc.publisher.place8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
dcterms.isPartOf.abbreviationMol. Biol. Cell
dcterms.oaStatusGreen Published, hybrid, Green Submitted
crisitem.author.deptFB 05 - Biologie/Chemie-
crisitem.author.deptidfb05-
crisitem.author.orcid0000-0003-0101-1257-
crisitem.author.parentorgUniversität Osnabrück-
crisitem.author.netidJuWo587-
crisitem.author.netidBrRo587-
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