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. 2020 Jun 16:12:22.
doi: 10.3389/fnsyn.2020.00022. eCollection 2020.

Palmitoylated Proteins in Dendritic Spine Remodeling

Joseph P Albanesi  1 , Barbara Barylko  1 , George N DeMartino  2 , David M Jameson  3
Affiliations

Palmitoylated Proteins in Dendritic Spine Remodeling

Joseph P Albanesi et al. Front Synaptic Neurosci. .

Abstract

Activity-responsive changes in the actin cytoskeleton are required for the biogenesis, motility, and remodeling of dendritic spines. These changes are governed by proteins that regulate the polymerization, depolymerization, bundling, and branching of actin filaments. Thus, processes that have been extensively characterized in the context of non-neuronal cell shape change and migration are also critical for learning and memory. In this review article, we highlight actin regulatory proteins that associate, at least transiently, with the dendritic plasma membrane. All of these proteins have been shown, either in directed studies or in high-throughput screens, to undergo palmitoylation, a potentially reversible, and stimulus-dependent cysteine modification. Palmitoylation increases the affinity of peripheral proteins for the membrane bilayer and contributes to their subcellular localization and recruitment to cholesterol-rich membrane microdomains.

Keywords: actin assembly; cytoskeletal remodeling; dendritic spines; palmitoylation; synaptic plasticity.

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Figures

Figure 1
Figure 1
Regulation of actin organization by Rho family GTPases. Rac and Cdc42 promote F-actin polymerization via stimulation of p21-activated kinases (PAKs), which phosphorylate and activate LIM kinase-1 (LIMK1). Rho activates LIMK1 by stimulating its downstream kinase ROCK, which phosphorylates LIMK1 directly. Active LIMK1 inhibits cofilin-mediated severing of actin filaments by phosphorylating cofilin on serine-3. Cofilin is re-activated upon dephosphorylation of serine-3 by the phosphatase, slingshot (SSH). SSH is inactivated by CaMKII-mediated phosphorylation, triggered by high-frequency stimulation (HFS) and re-activated upon dephosphorylation by calcineurin, triggered by low-frequency stimulation (LFS). Rac and Cdc42 promote actin branching by activating the nucleation promoting complexes WAVE and WASP, which stimulate the actin filament nucleating activity of the Arp2/3 complex. Rac activation of WAVE is facilitated by binding to the adaptor, IRSp53.
Figure 2
Figure 2
C-terminal sequences of Cdc42 variants and Rac1. Prenylated cysteines are highlighted in orange; palmitoylated cysteines are highlighted in yellow. Note that C188 in Cdc42Palm can undergo both prenylation and palmitoylation. Polybasic motifs are in bold.
Figure 3
Figure 3
Scheme of Arc/Arg3.1 showing N-terminal helical segments H1 and H2 and the HIV capsid-like domain. Shown above the scheme are the predicted coiled-coil (CC) motif and determinants of interactions with endophilins (Endo 2/3), presenilin-1 (PS-1), clathrin adaptor protein 2 (AP-2), Dynamin 2 (Dyn2), Ca2+/calmodulin-dependent kinase II (CaMKII), and transmembrane AMPAR regulatory protein γ2 (TARP γ2, also known as Stargazin). The palmitoylation motif is shown below the scheme.
Figure 4
Figure 4
Scheme showing Arc function in membrane vesiculation. Arc interacts directly with four proteins implicated in endocytosis of AMPA receptors: Dynamin 2, Endophilin, AP-2, and PICK1. Both Arc and PICK1 are palmitoylated in neurons. Recently, Arc has also been reported to promote the release of vesicles that contain Arc mRNA.
Figure 5
Figure 5
Scheme of PICK1. The PDZ domain mediates numerous functional PICK1-protein interactions, including with the AMPA receptor. The BAR domain is required for the association of PICK1 with membranes but also engages in protein interactions with Arc and with the GTPase domain of dynamin 2. Approximately 5–10% of PICK1 is palmitoylated on cysteine 414.
Figure 6
Figure 6
Structural features of TSPAN7. Like other tetraspanins, TSPAN7 contains four transmembrane domains, one large and one small extracellular region, and three small cytoplasmic segments. The C-terminal segment contains a PDZ-binding motif that interacts with PICK1.
Figure 7
Figure 7
Hypothetical scheme showing assembly of the actin regulatory machinery in the dendritic spine. Rac and Cdc42 bind to the plasma membrane (PM) via C-terminal prenylation and, in some cases, palmitoylation. They then recruit the WAVE and WASP complexes to the PM, where they stimulate Arp2/3-mediated actin filament branching from the PSD. Rac activation of WAVE is facilitated by IRSp53, which binds to membranes directly but is not known to undergo lipidation. Cdc42 can also bind to IRSp53, promoting the formation of a Cdc42/IRSp53/VASP complex. This complex induces actin filament elongation (by VASP) and membrane deformation (by IRSp53; Disanza et al., 2013), perhaps resulting in the formation of filopodia-like extensions from regions adjacent to the PSD (Chazeau et al., 2014). Arc, which is preferentially targeted to lipid rafts by palmitoylation, binds to both WAVE and IRSp53, which may partially account for its reported participation in both long-term potentiation (LTP) and spine enlargement and long-term depression (LTD) and spine shrinkage. Although this model is highly speculative, it depicts many of the interactions described in this review.
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References

    1. Ali M. R., Cheng K. H., Huang J. (2007). Assess the nature of cholesterol-lipid interactions through the chemical potential of cholesterol in phosphatidylcholine bilayers. Proc. Natl. Acad. Sci. U S A 104, 5372–5377. 10.1073/pnas.0611450104 - DOI - PMC - PubMed
    1. Anastasiadis P. Z. (2007). p120-ctn: a nexus for contextual signaling via Rho GTPases. Biochim. Biophys. Acta 1773, 34–46. 10.1016/j.bbamcr.2006.08.040 - DOI - PubMed
    1. Anastasiadis P. Z., Moon S. Y., Thoreson M. A., Mariner D. J., Crawford H. C., Zheng Y., et al. (2000). Inhibition of RhoA by p120 catenin. Nat. Cell Biol. 2, 637–644. 10.1038/35023588 - DOI - PubMed
    1. Antonny B., Burd C., De Camilli P., Chen E., Daumke O., Faelber K., et al. . (2016). Membrane fission by dynamin: what we know and what we need to know. EMBO J. 35, 2270–2284. 10.15252/embj.201694613 - DOI - PMC - PubMed
    1. Arstikaitis P., Gauthier-Campbell C., Carolina Gutierrez Herrera R., Huang K., Levinson J. N., Murphy T. H., et al. . (2008). Paralemmin-1, a modulator of filopodia induction is required for spine maturation. Mol. Biol. Cell 19, 2026–2038. 10.1091/mbc.e07-08-0802 - DOI - PMC - PubMed

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