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The Rufys, a Family of Effector Proteins Involved in Intracellular Trafficking and Cytoskeleton Dynamics Rémy Char, Philippe Pierre

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The Rufys, a Family of Effector Proteins Involved in Intracellular Trafficking and Cytoskeleton Dynamics Rémy Char, Philippe Pierre The RUFYs, a Family of Effector Proteins Involved in Intracellular Trafficking and Cytoskeleton Dynamics Rémy Char, Philippe Pierre To cite this version: Rémy Char, Philippe Pierre. The RUFYs, a Family of Effector Proteins Involved in Intracellular Trafficking and Cytoskeleton Dynamics. Frontiers in Cell and Developmental Biology, Frontiers media, 2020, 8, 10.3389/fcell.2020.00779. hal-02988643 HAL Id: hal-02988643 https://hal.archives-ouvertes.fr/hal-02988643 Submitted on 4 Nov 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. fcell-08-00779 August 9, 2020 Time: 12:3 # 1 REVIEW published: 11 August 2020 doi: 10.3389/fcell.2020.00779 The RUFYs, a Family of Effector Proteins Involved in Intracellular Trafficking and Cytoskeleton Dynamics Rémy Char1* and Philippe Pierre1,2,3* 1 Aix Marseille Université, Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale, Centre d’Immunologie de Marseille-Luminy, Marseille, France, 2 Institute for Research in Biomedicine and Ilidio Pinho Foundation, Department of Medical Sciences, University of Aveiro, Aveiro, Portugal, 3 Shanghai Institute of Immunology, School of Medicine, Shanghai Jiao Tong University, Shanghai, China Intracellular trafficking is essential for cell structure and function. In order to perform key tasks such as phagocytosis, secretion or migration, cells must coordinate their intracellular trafficking, and cytoskeleton dynamics. This relies on certain classes of proteins endowed with specialized and conserved domains that bridge membranes with effector proteins. Of particular interest are proteins capable of interacting with Edited by: membrane subdomains enriched in specific phosphatidylinositol lipids, tightly regulated Roberto Botelho, Ryerson University, Canada by various kinases and phosphatases. Here, we focus on the poorly studied RUFY family Reviewed by: of adaptor proteins, characterized by a RUN domain, which interacts with small GTP- Daniel G. S. Capelluto, binding proteins, and a FYVE domain, involved in the recognition of phosphatidylinositol Virginia Tech, United States Brian Paul Ceresa, 3-phosphate. We report recent findings on this protein family that regulates endosomal University of Louisville, United States trafficking, cell migration and upon dysfunction, can lead to severe pathology at the *Correspondence: organismal level. Rémy Char [email protected] Keywords: RUFY, cancer, neurodegenerative diseases, immunity, RUN, FYVE, phosphatidylinositol 3-phosphate, Philippe Pierre cytoskeleton [email protected] Specialty section: INTRODUCTION This article was submitted to Membrane Traffic, The organization of cells into multiple membranous compartments with specific biochemical a section of the journal functions requires complex intracellular traffic and sorting of lipids and proteins, to transport them Frontiers in Cell and Developmental from their sites of synthesis to their functional destination. Intracellular transport involves lipid Biology vesicles or tubules with the capacity to fuse with one another or to be secreted. They collectively Received: 11 June 2020 participate in the dynamic exchanges necessary for cell homeostasis (Rothman, 2002; Søreng Accepted: 24 July 2020 et al., 2018). Membrane traffic is tightly coordinated with protein synthesis, signal transduction of Published: 11 August 2020 environmental stimuli and cytoskeleton organization, allowing the implementation of key cellular Citation: functions such as endocytosis, exocytosis, or migration (McMahon and Gallop, 2005; Habtezion Char R and Pierre P (2020) The et al., 2016; Vega-Cabrera and Pardo-López, 2017; MacGillavry and Hoogenraad, 2018; Margaria RUFYs, a Family of Effector Proteins Involved in Intracellular Trafficking et al., 2019; Tapia et al., 2019; Buratta et al., 2020; Stalder and Gershlick, 2020). and Cytoskeleton Dynamics. Several families of molecular components required for orchestrating membrane vesicle exchange Front. Cell Dev. Biol. 8:779. and transport during this process are conserved. They include adaptor and coat proteins, small doi: 10.3389/fcell.2020.00779 GTP-binding proteins (GTPases), as well as Synaptosome Associated Protein (SNAP) Receptor Frontiers in Cell and Developmental Biology| www.frontiersin.org 1 August 2020| Volume 8| Article 779 fcell-08-00779 August 9, 2020 Time: 12:3 # 2 Char and Pierre RUFYs Proteins and Trafficking (SNARE) proteins and SNARE binding proteins (Juliano, 2018). other trafficking events (Naslavsky and Caplan, 2018; Figure 1B). The vast superfamily of GTPases is involved in the establishment On their way to degradation, sorted cargo accumulate in or regulation of virtually every step of intracellular membrane early endosomes (EE), that further mature into late endosomes trafficking. They behave as molecular switches that can alternate (LE) through multiple events of cargo and lipid sorting. between active and inactive states, through GTP binding and Late endosomes adopt a membrane organization termed hydrolysis into GDP (Takai et al., 2001; Stenmark, 2009). The multivesicular bodies, that are enriched in lysobisphosphatidic largest group of GTPases involved in intracellular membrane acid and contain intraluminal vesicles (Gruenberg, 2020). Next, traffic is the Rab proteins family (Lamb et al., 2016). Rab GTPases LE potentiate their hydrolytic competence by fusing with specifically localize to different intracellular compartments, lysosomes (Pillay et al., 2002) resulting in the degradation regulating vesicle formation and sorting, as well as transport of their contents, providing nutrients and key factors to along the cytoskeletal network. Each Rab protein can be recruited the cell (Doherty and McMahon, 2009; Kaksonen and Roux, to specific membrane subdomains of a defined organelle and 2018). Notably, endosomes play a role in signal transduction is associated to multiple effectors controlling membrane fusion by serving as signaling platforms either for surface activated and trafficking. Rab interaction with the membrane fusion receptors like Toll-like receptors and epidermal growth factor complexes and cytoskeleton regulators is therefore crucial for receptor or metabolic sensors such as mechanistic target cellular functions, including endocytosis and autophagy (Chen of rapamycin complex 1 (mTORC1; Argüello et al., 2016). and Wandinger-Ness, 2001; Bruce et al., 2010; Geng et al., 2010; Often they promote the degradation of their targets, leading Thomas and Fromme, 2020; Yuan and Song, 2020). to signal termination (Chung et al., 2010). The endocytic Here, we review the literature concerning a less-well known pathway has also specialized functions in differentiated cells family of proteins involved in the complex biochemical crosstalk such as neurotransmitter release and recycling in neurons, or established between the cytoskeleton and intracellular vesicles. antigen processing and presentation in professional antigen This small group of proteins was named RUFY for “RUN and presenting cells, like B cells or dendritic cells (Argüello FYVE domain-containing.” RUFYs share a common structural et al., 2016; Solé-Domènech et al., 2016; Hinze and Boucrot, domain organization, including an N-terminal RUN domain, 2018). Endocytosis events and endosomes positioning is one or several coiled-coil (CC) repeats and a C-terminal FYVE highly dependent on the dynamic and spatial re-organization domain (Figure 1A). The molecular structures of the different of the different cytoskeleton networks that include actin, RUFY proteins has been described (Dunkelberg and Gutierrez- intermediate filaments, or microtubules (Fletcher and Mullins, Hartmann, 2001; Mari et al., 2001; Kukimoto-Niino et al., 2006; 2010; Pegoraro et al., 2017). Kitagishi and Matsuda, 2013), but their function in endocytic Complementary to endocytosis, autophagy is an intracellular regulation and their physiological relevance at the organismal process by which cells degrade and recycle their own cytoplasmic level are still poorly characterized (Kitagishi and Matsuda, 2013; materials (Mizushima and Komatsu, 2011). Autophagy plays a Terawaki et al., 2016). We revisit here how the rufy gene central role in many physiological processes including stress family was annotated, and propose the addition of a novel management, development, immunity and aging (Puleston and member, the fyco1 (FYVE and Coiled-coil containing domain Simon, 2014; Zhong et al., 2016; Fîlfan et al., 2017; Moretti 1) gene given its sequence and functional similarities with et al., 2017; Doherty and Baehrecke, 2018). Autophagy is the other rufy genes (Pankiv et al., 2010; Terawaki et al., partially controlled though mTORC1 activity and is responsible 2015). We also highlight recent findings on the implication of for degradation and recycling of misfolded proteins, as well RUFY proteins in the regulation of cytoskeleton and endosome as obsolete organelles (Galluzzi et al., 2017). The endpoint of dynamics and their contribution to immunity, cancer and autophagy is to deliver cytoplasmic material to lysosomes,
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