{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n KIF21B is a member of the kinesin‐4 family of plus end–directed motor proteins that plays multifaceted roles in regulating microtubule dynamics and intracellular transport. In neurons, KIF21B acts as a processive motor that accumulates at microtubule plus ends and induces pausing through non‐motor microtubule‐binding domains in its stalk and WD40 tail, thereby restricting filament growth and modulating dendritic architecture. Loss of KIF21B function in neuronal models is associated with reduced dendritic arbor complexity, lower spine density, impaired synaptic transmission, and deficits in synaptic plasticity—including alterations in NMDA receptor–dependent long‐term depression and fear extinction—which in turn contribute to cognitive dysfunction."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in shaping dendritic structure and synaptic function, KIF21B influences receptor trafficking in neurons. It participates in the delivery of critical postsynaptic cargoes such as GABA_A receptors, and its interaction with proteins like NBEA and TRIM3 helps regulate local receptor recycling and motor motility, thereby contributing to the fine‐tuning of synaptic efficacy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its neuronal functions, KIF21B has important roles in immune cells. In T lymphocytes, for example, KIF21B helps regulate microtubule length to ensure proper centrosome translocation during immunological synapse formation—a process critical for efficient T cell polarization and activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic association studies have consistently linked KIF21B polymorphisms with increased susceptibility to autoimmune conditions such as multiple sclerosis, inflammatory bowel disease, and ankylosing spondylitis in diverse populations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "12"}]}, {"type": "t", "text": " Moreover, rare missense variants in KIF21B are associated with neurodevelopmental disorders characterized by brain malformations and connectivity deficits, underscoring its critical role in early neuronal development."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, abnormal regulation of KIF21B expression is emerging as a factor in tumor biology; for instance, in gastric cancer, upregulation of KIF21B driven by diminished miR‐132–3p levels correlates with enhanced tumor cell proliferation, migration, invasion, and activation of Wnt/β‐catenin signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies highlight that KIF21B integrates motor activity and microtubule regulation to control neuronal morphology and synaptic function as well as immune cell polarization, with genetic variants and expression changes contributing to disease susceptibility and progression.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mary Muhia, Edda Thies, Dorthe Labonté, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Kinesin KIF21B Regulates Microtubule Dynamics and Is Essential for Neuronal Morphology, Synapse Function, and Learning and Memory."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2016.03.086"}], "href": "https://doi.org/10.1016/j.celrep.2016.03.086"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27117409"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27117409"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Wilhelmina E van Riel, Ankit Rai, Sarah Bianchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kinesin-4 KIF21B is a potent microtubule pausing factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.24746"}], "href": "https://doi.org/10.7554/eLife.24746"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28290984"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28290984"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Momo Morikawa, Yosuke Tanaka, Hyun-Soo Cho, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Molecular Motor KIF21B Mediates Synaptic Plasticity and Fear Extinction by Terminating Rac1 Activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2018.05.089"}], "href": "https://doi.org/10.1016/j.celrep.2018.05.089"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29949770"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29949770"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Kira V Gromova, Mary Muhia, Nicola Rothammer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2018.04.112"}], "href": "https://doi.org/10.1016/j.celrep.2018.04.112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29847800"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29847800"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dorthe Labonté, Edda Thies, Yvonne Pechmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TRIM3 regulates the motility of the kinesin motor protein KIF21B."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0075603"}], "href": "https://doi.org/10.1371/journal.pone.0075603"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24086586"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24086586"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Dorthe Labonté, Edda Thies, Matthias Kneussel "}, {"type": "b", "children": [{"type": "t", "text": "The kinesin KIF21B participates in the cell surface delivery of γ2 subunit-containing GABAA receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejcb.2014.07.007"}], "href": "https://doi.org/10.1016/j.ejcb.2014.07.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25172774"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25172774"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Supriya Swarnkar, Yosef Avchalumov, Bindu L Raveendra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kinesin Family of Proteins Kif11 and Kif21B Act as Inhibitory Constraints of Excitatory Synaptic Transmission Through Distinct Mechanisms."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-018-35634-7"}], "href": "https://doi.org/10.1038/s41598-018-35634-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30479371"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30479371"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Peter Jan Hooikaas, Hugo Gj Damstra, Oane J Gros, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kinesin-4 KIF21B limits microtubule growth to allow rapid centrosome polarization in T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.62876"}], "href": "https://doi.org/10.7554/eLife.62876"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33346730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33346730"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Patrick Danoy, Karena Pryce, Johanna Hadler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of variants at 1q32 and STAT3 with ankylosing spondylitis suggests genetic overlap with Crohn's disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1001195"}], "href": "https://doi.org/10.1371/journal.pgen.1001195"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21152001"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21152001"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Unknown Authors "}, {"type": "b", "children": [{"type": "t", "text": "Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddp542"}], "href": "https://doi.org/10.1093/hmg/ddp542"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20007504"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20007504"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "A Goris, S Boonen, M-B D'hooghe, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Replication of KIF21B as a susceptibility locus for multiple sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Med Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1136/jmg.2009.075911"}], "href": "https://doi.org/10.1136/jmg.2009.075911"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20587413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20587413"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Xinglin Yang, Ming Li, Liya Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association of KIF21B genetic polymorphisms with ankylosing spondylitis in a Chinese Han population of Shandong Province."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Rheumatol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10067-014-2761-5"}], "href": "https://doi.org/10.1007/s10067-014-2761-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25149646"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25149646"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Laure Asselin, José Rivera Alvarez, Solveig Heide, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in the KIF21B kinesin gene cause neurodevelopmental disorders through imbalanced canonical motor activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-020-16294-6"}], "href": "https://doi.org/10.1038/s41467-020-16294-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32415109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32415109"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "Bingtian Liu, Ling Qiang, Bingxin Guan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting kinesin family member 21B by miR-132-3p represses cell proliferation, migration and invasion in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Bioengineered (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/21655979.2022.2054755"}], "href": "https://doi.org/10.1080/21655979.2022.2054755"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35341446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35341446"}]}]}]}