{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRab35 is a small GTPase that acts as a master regulator of membrane trafficking events essential for the proper execution of cytokinesis. In dividing cells, Rab35 modulates a rapid endocytic recycling pathway that governs the localization of phosphatidylinositol 4,5‐bisphosphate and septin proteins at the intercellular bridge, thereby ensuring bridge stability and timely abscission. In addition, Rab35 is recruited to sites of endocytosis where it directs factors such as OCRL and MICAL1 to remodel the actin cytoskeleton at the midbody. Its activation is controlled by several guanine nucleotide exchange factors—including DENND1B, connecdenn 3, and DENND2B—whose interactions with Rab35 have been elucidated by high‐resolution structural studies, and by regulators that orchestrate its precise loading on newborn endosomes and the cytokinetic bridge."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its critical role in cytokinesis, Rab35 regulates key aspects of cell surface dynamics and signal transduction. In T lymphocytes, Rab35 contributes to immunological synapse formation by ensuring the proper polarized transport of the T-cell receptor and recycling markers. In epithelial cells, it maintains cell–cell adhesion by stabilizing cadherin at the plasma membrane while simultaneously suppressing Arf6‐dependent recycling pathways that modulate integrin and growth factor receptor levels. Furthermore, Rab35 influences directional cell migration via crosstalk with Rac1 and is capable of stimulating PI3K/AKT signaling cascades, thereby linking its trafficking functions to oncogenic transformation. Comprehensive reviews have underscored the diverse roles of Rab35 in endosomal trafficking, exosome release, phagocytosis, and neurite outgrowth."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRab35 also participates in a variety of other cellular processes that underscore its multifunctional character. It modulates actin filament assembly by recruiting actin‐bundling proteins such as fascin, and its dynamic regulation is critical during phagocytosis where oscillations in Rab35 and its interplay with Arf6 and the effector ACAP2 ensure efficient uptake of extracellular particles. Moreover, Rab35 directs selective cargo through autophagic pathways by recruiting the autophagy receptor NDP52, and structural studies have provided atomic‐level details of its interactions with key effectors. Aberrant Rab35 activity has been linked with oncogenic settings—notably in the context of resistant cancer phenotypes where altered exosome secretion is observed—and a mutation in Rab35 has been implicated in neurodevelopmental disorders. In addition, its binding to regulators like PRPK further influences p53 transcriptional activity, emphasizing the broad impact of Rab35 in cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "22"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ilektra Kouranti, Martin Sachse, Nassim Arouche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab35 regulates an endocytic recycling pathway essential for the terminal steps of cytokinesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2006.07.020"}], "href": "https://doi.org/10.1016/j.cub.2006.07.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16950109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16950109"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Daphné Dambournet, Mickael Machicoane, Laurent Chesneau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab35 GTPase and OCRL phosphatase remodel lipids and F-actin for successful cytokinesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb2279"}], "href": "https://doi.org/10.1038/ncb2279"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21706022"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21706022"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Xudong Wu, Michael J Bradley, Yiying Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insights regarding guanine nucleotide exchange from the structure of a DENN-domain protein complexed with its Rab GTPase substrate."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1110415108"}], "href": "https://doi.org/10.1073/pnas.1110415108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22065758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22065758"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Andrea L Marat, Maria S Ioannou, Peter S McPherson "}, {"type": "b", "children": [{"type": "t", "text": "Connecdenn 3/DENND1C binds actin linking Rab35 activation to the actin cytoskeleton."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E11-05-0474"}], "href": "https://doi.org/10.1091/mbc.E11-05-0474"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22072793"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22072793"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Clothilde Cauvin, Morgane Rosendale, Neetu Gupta-Rossi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab35 GTPase Triggers Switch-like Recruitment of the Lowe Syndrome Lipid Phosphatase OCRL on Newborn Endosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cub.2015.11.040"}], "href": "https://doi.org/10.1016/j.cub.2015.11.040"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26725203"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26725203"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Stéphane Frémont, Hussein Hammich, Jian Bai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oxidation of F-actin controls the terminal steps of cytokinesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms14528"}], "href": "https://doi.org/10.1038/ncomms14528"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28230050"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28230050"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Nicholas V G Iannantuono, Gregory Emery "}, {"type": "b", "children": [{"type": "t", "text": "Rab11FIP1 maintains Rab35 at the intercellular bridge to promote actin removal and abscission."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.244384"}], "href": "https://doi.org/10.1242/jcs.244384"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34152390"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34152390"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Rahul Kumar, Vincent Francis, Maria S Ioannou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DENND2B activates Rab35 at the intercellular bridge, regulating cytokinetic abscission and tetraploidy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2023.112795"}], "href": "https://doi.org/10.1016/j.celrep.2023.112795"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37454296"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37454296"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Genaro Patino-Lopez, Xiaoyun Dong, Khadija Ben-Aissa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab35 and its GAP EPI64C in T cells regulate receptor recycling and immunological synapse formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M800056200"}], "href": "https://doi.org/10.1074/jbc.M800056200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18450757"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18450757"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Patrick D Allaire, Mohamed Seyed Sadr, Mathilde Chaineau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interplay between Rab35 and Arf6 controls cargo recycling to coordinate cell adhesion and migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.112375"}], "href": "https://doi.org/10.1242/jcs.112375"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23264734"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23264734"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Yichao Zhu, Tian Shen, Jiaojing Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab35 is required for Wnt5a/Dvl2-induced Rac1 activation and cell migration in MCF-7 breast cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2013.01.015"}], "href": "https://doi.org/10.1016/j.cellsig.2013.01.015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23353182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23353182"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Dipannita Dutta, Julie G Donaldson "}, {"type": "b", "children": [{"type": "t", "text": "Sorting of Clathrin-Independent Cargo Proteins Depends on Rab35 Delivered by Clathrin-Mediated Endocytosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/tra.12302"}], "href": "https://doi.org/10.1111/tra.12302"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25988331"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25988331"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Douglas B Wheeler, Roberto Zoncu, David E Root, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of an oncogenic RAB protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.aaa4903"}], "href": "https://doi.org/10.1126/science.aaa4903"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26338797"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26338797"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Kerstin Klinkert, Arnaud Echard "}, {"type": "b", "children": [{"type": "t", "text": "Rab35 GTPase: A Central Regulator of Phosphoinositides and F-actin in Endocytic Recycling and Beyond."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Traffic (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/tra.12422"}], "href": "https://doi.org/10.1111/tra.12422"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27329675"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27329675"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Yasuhito Abe, Takashi Takeuchi, Yoshinori Imai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Small Ras-like protein Ray/Rab1c modulates the p53-regulating activity of PRPK."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2006.03.071"}], "href": "https://doi.org/10.1016/j.bbrc.2006.03.071"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16600182"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16600182"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Jun Zhang, Marko Fonovic, Kaye Suyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab35 controls actin bundling by recruiting fascin as an effector protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1174921"}], "href": "https://doi.org/10.1126/science.1174921"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19729655"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19729655"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Youhei Egami, Makoto Fujii, Katsuhisa Kawai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation-Inactivation Cycling of Rab35 and ARF6 Is Required for Phagocytosis of Zymosan in RAW264 Macrophages."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol Res (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1155/2015/429439"}], "href": "https://doi.org/10.1155/2015/429439"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26229970"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26229970"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Anja Biesemann, Alexandra Gorontzi, Francis Barr, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab35 protein regulates evoked exocytosis of endothelial Weibel-Palade bodies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.773333"}], "href": "https://doi.org/10.1074/jbc.M116.773333"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28566286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28566286"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Atsuko Minowa-Nozawa, Takashi Nozawa, Keiko Okamoto-Furuta, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab35 GTPase recruits NDP52 to autophagy targets."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201796463"}], "href": "https://doi.org/10.15252/embj.201796463"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28848034"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28848034"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Salvatore Corallino, Chiara Malinverno, Beate Neumann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A RAB35-p85/PI3K axis controls oscillatory apical protrusions required for efficient chemotactic migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-03571-8"}], "href": "https://doi.org/10.1038/s41467-018-03571-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29662076"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29662076"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Chao Li, Zhishuang Gao, Zhiwei Cui, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deubiquitylation of Rab35 by USP32 promotes the transmission of imatinib resistance by enhancing exosome secretion in gastrointestinal stromal tumours."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-023-02600-1"}], "href": "https://doi.org/10.1038/s41388-023-02600-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36725886"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36725886"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Murielle P Serres, Ronan Shaughnessy, Sophie Escot, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MiniBAR/GARRE1 is a dual Rac and Rab effector required for ciliogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Cell (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.devcel.2023.09.010"}], "href": "https://doi.org/10.1016/j.devcel.2023.09.010"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37875118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37875118"}]}]}]}