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

Gauthier-Kemper A, Igaev M, Sündermann F, Janning D, Brühmann J, Moschner K, Reyher HJ, Junge W, Glebov K, Walter J, Bakota L, Brandt R - Mol. Biol. Cell (2014)

Bottom Line: Plasma membrane association decreased the diffusion constant fourfold in neuritic shafts.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, University of Osnabrück, 49076 Osnabrück, Germany.

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Schematic representation summarizing our results, demonstrating the interplay of phosphorylation (P) and palmitoylation (L) in plasma membrane targeting and sorting of GAP43. The data indicate that phosphorylation at Ser-41 serves as a switch to regulate local diffusion by inducing plasma membrane association of lipidated GAP43, whereas palmitoylation tags a fraction of proteins for global sorting by inducing piggybacking on exocytic vesicles.
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Figure 9: Schematic representation summarizing our results, demonstrating the interplay of phosphorylation (P) and palmitoylation (L) in plasma membrane targeting and sorting of GAP43. The data indicate that phosphorylation at Ser-41 serves as a switch to regulate local diffusion by inducing plasma membrane association of lipidated GAP43, whereas palmitoylation tags a fraction of proteins for global sorting by inducing piggybacking on exocytic vesicles.

Mentions: Posttranslational modifications can dramatically change the function and interactions of cytosolic proteins and are likely to contribute to protein sorting. This is of particular importance for highly polarized cells such as neurons. An instructive example is GAP43, which is synthesized on free ribosomes in the neuronal cell body, is susceptible to phosphorylation and lipidation, and becomes highly enriched in the tips of extending neurites. To scrutinize how phosphorylation and lipidation mediate sorting of GAP43, we used a combination of biochemical, genetic, and imaging approaches. Our results are summarized in Figure 9 and demonstrate a complex interplay of phosphorylation and palmitoylation in plasma membrane targeting and sorting of GAP43. In particular, we showed that 1) phosphorylation at Ser-41 directs palmitoylated GAP43 to the plasma membrane, 2) plasma membrane association decreases diffusion of GAP43 in the cell body and neuritic shaft, and 3) S-palmitoylation tags GAP43 for global sorting by inducing piggybacking on exocytic vesicles. Furthermore, we showed that plasma membrane association exhibits an absolute requirement for palmitoylation and that palmitoylation-mediated sorting to the growth cone is increased by phosphorylation-mediated membrane reaction.


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

Gauthier-Kemper A, Igaev M, Sündermann F, Janning D, Brühmann J, Moschner K, Reyher HJ, Junge W, Glebov K, Walter J, Bakota L, Brandt R - Mol. Biol. Cell (2014)

Schematic representation summarizing our results, demonstrating the interplay of phosphorylation (P) and palmitoylation (L) in plasma membrane targeting and sorting of GAP43. The data indicate that phosphorylation at Ser-41 serves as a switch to regulate local diffusion by inducing plasma membrane association of lipidated GAP43, whereas palmitoylation tags a fraction of proteins for global sorting by inducing piggybacking on exocytic vesicles.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4214776&req=5

Figure 9: Schematic representation summarizing our results, demonstrating the interplay of phosphorylation (P) and palmitoylation (L) in plasma membrane targeting and sorting of GAP43. The data indicate that phosphorylation at Ser-41 serves as a switch to regulate local diffusion by inducing plasma membrane association of lipidated GAP43, whereas palmitoylation tags a fraction of proteins for global sorting by inducing piggybacking on exocytic vesicles.
Mentions: Posttranslational modifications can dramatically change the function and interactions of cytosolic proteins and are likely to contribute to protein sorting. This is of particular importance for highly polarized cells such as neurons. An instructive example is GAP43, which is synthesized on free ribosomes in the neuronal cell body, is susceptible to phosphorylation and lipidation, and becomes highly enriched in the tips of extending neurites. To scrutinize how phosphorylation and lipidation mediate sorting of GAP43, we used a combination of biochemical, genetic, and imaging approaches. Our results are summarized in Figure 9 and demonstrate a complex interplay of phosphorylation and palmitoylation in plasma membrane targeting and sorting of GAP43. In particular, we showed that 1) phosphorylation at Ser-41 directs palmitoylated GAP43 to the plasma membrane, 2) plasma membrane association decreases diffusion of GAP43 in the cell body and neuritic shaft, and 3) S-palmitoylation tags GAP43 for global sorting by inducing piggybacking on exocytic vesicles. Furthermore, we showed that plasma membrane association exhibits an absolute requirement for palmitoylation and that palmitoylation-mediated sorting to the growth cone is increased by phosphorylation-mediated membrane reaction.

Bottom Line: Plasma membrane association decreased the diffusion constant fourfold in neuritic shafts.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurobiology, University of Osnabrück, 49076 Osnabrück, Germany.

Show MeSH
Related in: MedlinePlus