S-Palmitoylation of Tyrosinase at Cysteine500 Regulates Melanogenesis

Niki, Yoko; Adachi, Naoko; Fukata, Masaki; Fukata, Yuko; Oku, Shinichiro; Makino-Okamura, Chieko; Takeuchi, Seiji; Wakamatsu, Kazumasa; Itô, Shôsuke; Declercq, L.; Yarosh, Daniel B.; Mammone, T.; Nishigori, Chikako; Saito, Naoaki; Ueyama, Takeshi

doi:10.1016/j.jid.2022.08.040

Cited by 9 publications

(8 citation statements)

References 48 publications

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“…Thus, the synchronized Tyr transport system that we established in this study should provide an ideal tool to determine whether Rab32/38 are involved in Tyr transport to immature melanosomes, VAMP7 recycling from melanosomes, or both by using appropriate endosome markers in combination with live-cell imaging. It will also be possible to evaluate the significance of post-translational modifications such as palmitoylation of Tyr 34 and ubiquitylation 35 , 36 in Tyr transport by using Tyr-EGFP-FM4 mutants lacking post-translational modification sites. In addition to using the synchronized Tyr transport system to re-assess or re-investigate known regulators or modifications of Tyr, it can be applied to the search for new Tyr transport regulators by performing siRNA screening or CRISPR/Cas9-mediated genome-wide screening in the future.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a synchronized tyrosinase transport system revealed a role of Tyrp1 in efficient melanogenesis by promoting tyrosinase targeting to melanosomes

Nakamura,

Fukuda

2024

Sci Rep

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Tyrosinase (Tyr) is a key enzyme in the process of melanin synthesis that occurs exclusively within specialized organelles called melanosomes in melanocytes. Tyr is synthesized and post-translationally modified independently of the formation of melanosome precursors and then transported to immature melanosomes by a series of membrane trafficking events that includes endoplasmic reticulum (ER)-to-Golgi transport, post-Golgi trafficking, and endosomal transport. Although several important regulators of Tyr transport have been identified, their precise role in each Tyr transport event is not fully understood, because Tyr is present in several melanocyte organelles under steady-state conditions, thereby precluding the possibility of determining where Tyr is being transported at any given moment. In this study, we established a novel synchronized Tyr transport system in Tyr-knockout B16-F1 cells by using Tyr tagged with an artificial oligomerization domain FM4 (named Tyr-EGFP-FM4). Tyr-EGFP-FM4 was initially trapped at the ER under oligomerized conditions, but at 30 min after chemical dissociation into monomers, it was transported to the Golgi and at 9 h reached immature melanosomes. Melanin was then detected at 12 h after the ER exit of Tyr-EGFP-FM4. By using this synchronized Tyr transport system, we were able to demonstrate that Tyr-related protein 1 (Tyrp1), another melanogenic enzyme, is a positive regulator of efficient Tyr targeting to immature melanosomes. Thus, the synchronized Tyr transport system should serve as a useful tool for analyzing the molecular mechanism of each Tyr transport event in melanocytes as well as in the search for new drugs or cosmetics that artificially regulate Tyr transport.

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Section: Discussionmentioning

confidence: 99%

Establishment of a synchronized tyrosinase transport system revealed a role of Tyrp1 in efficient melanogenesis by promoting tyrosinase targeting to melanosomes

Nakamura,

Fukuda

2024

Sci Rep

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“…The role of Golgi-residing zDHHCs in neuronal cells has also been demonstrated. Among zDHHCs, zDHHC3 is stably localized in the Golgi apparatus ( Niki et al, 2023 ). JAK1 palmitoylation is important for neuronal cell medium-dependent signaling and neuronal survival, and zDHHC3 or zDHHC7 can bind to palmitoylated JAK1 ( Hernandez et al, 2023 ).…”

Section: Role Of Zdhhcs In Neurobiologymentioning

confidence: 99%

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

Liao,

Huang,

Liu

et al. 2024

Front. Pharmacol.

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S-palmitoylation is a reversible posttranslational modification, and the palmitoylation reaction in human-derived cells is mediated by the zDHHC family, which is composed of S-acyltransferase enzymes that possess the DHHC (Asp-His-His-Cys) structural domain. zDHHC proteins form an autoacylation intermediate, which then attaches the fatty acid to cysteine a residue in the target protein. zDHHC proteins sublocalize in different neuronal structures and exert dif-ferential effects on neurons. In humans, many zDHHC proteins are closely related to human neu-rological disor-ders. This review focuses on a variety of neurological disorders, such as AD (Alz-heimer’s disease), HD (Huntington’s disease), SCZ (schizophrenia), XLID (X-linked intellectual disability), attention deficit hyperactivity disorder and glioma. In this paper, we will discuss and summarize the research progress regarding the role of zDHHC proteins in these neu-rological disorders.

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“…S-acylation is dynamic, but the duration of the cycles varies depending on the protein and the physiological state of the cell, from minutes to days-the latter one being quasi-equivalent to irreversible on the cellular time scale [58,59]. Removal of the acyl chain is carried out by ); conformational changes (e.g., voltage-gated channels [14][15][16]); multimerization (e.g., STING [34,35], Gasdermin D pores [36,37] preprints); lipid organization (e.g., microdomain association of LAT [28] and viral glycoproteins [27]); complex formation (e.g., ankyrin-G, GPCRs [20,21]); protein trafficking (e.g., Ras, integral membrane proteins [25,38,39]); signal transduction (NOD2 and Myd88 [17][18][19]); and crosstalk with other post-translational modifications (PTMs) (e.g., tyrosinase, BK potassium channels [30,31]). Cartoons were generated with Biorender.com poorly characterized acyl-protein thioesterases (APTs), members of the serine hydrolase superfamily [29].…”

Section: Acyl Protein Thioesterases Reverse S-acylationmentioning

confidence: 99%

“…2. These include modulation of protein conformation [12][13][14][15][16]; capacity to transduce signals [17][18][19]; ability to interact with other proteins [18,20,21]; regulation of their trafficking and localization [12,[22][23][24][25]; physicochemical properties of their transmembrane domains (TMDs) and their association with surrounding lipids [26][27][28]; and cross-talk with other PTMs [29][30][31]. By modifying such a vast number of proteins and affecting their function through a broad diversity of means, S-acylation is involved in various diseases, including neurodegenerative diseases, cancer, and inflammatory diseases (reviewed in [10,19,32]).…”

Section: Introductionmentioning

confidence: 99%

“…Consequences of protein S-acylation. Schematic representation of selected potential consequences of S-acylation on cytosolic and membranes proteins depicting examples of membrane association (e.g., Src kinases[33]); conformational changes (e.g., voltage-gated channels[14][15][16]); multimerization (e.g., STING[34,35], Gasdermin D pores[36,37] preprints); lipid organization (e.g., microdomain association of LAT[28] and viral glycoproteins[27]); complex formation (e.g., ankyrin-G, GPCRs[20,21]); protein trafficking (e.g., Ras, integral membrane proteins[25,38,39]); signal transduction (NOD2 and Myd88[17][18][19]); and crosstalk with other post-translational modifications (PTMs) (e.g., tyrosinase, BK potassium channels[30,31]). Cartoons were generated with Biorender.com…”

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confidence: 99%

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S‐acylation: an orchestrator of the life cycle and function of membrane proteins

Mesquita,

Abrami,

Samurkas

et al. 2023

The FEBS Journal

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S‐Acylation is a covalent post‐translational modification of proteins with fatty acids, achieved by enzymatic attachment via a labile thioester bond. This modification allows for dynamic control of protein properties and functions in association with cell membranes. This lipid modification regulates a substantial portion of the human proteome and plays an increasingly recognized role throughout the lifespan of affected proteins. Recent technical advancements have propelled the S‐acylation field into a "molecular era," unveiling new insights into its mechanistic intricacies and far‐reaching implications. With a striking increase in the number of studies on this modification, new concepts are indeed emerging on the roles for S‐acylation in specific cell biology processes and features. After a brief overview of the enzymes involved in S‐acylation, this viewpoint focuses on the importance of S‐acylation in the homeostasis, function, and coordination of integral membrane proteins. In particular, we put forward the hypotheses that S‐acylation is a gatekeeper of membrane protein folding and turnover and a regulator of the formation and dynamics of membrane contact sites.

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S-Palmitoylation of Tyrosinase at Cysteine500 Regulates Melanogenesis

Cited by 9 publications

References 48 publications

Establishment of a synchronized tyrosinase transport system revealed a role of Tyrp1 in efficient melanogenesis by promoting tyrosinase targeting to melanosomes

Establishment of a synchronized tyrosinase transport system revealed a role of Tyrp1 in efficient melanogenesis by promoting tyrosinase targeting to melanosomes

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

S‐acylation: an orchestrator of the life cycle and function of membrane proteins

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