{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Kinesin light chain 2 (KLC2) is a versatile component of the kinesin‐1 motor complex that confers cargo specificity and regulates microtubule‐based transport in a variety of cellular contexts. For example, phosphorylation of KLC2—triggered by AMPA receptor stimulation and mediated by kinases such as GSK‑3β—modulates the association between the motor complex and receptor‐containing vesicles, thereby influencing synaptic plasticity and even mood‐related behaviors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In parallel, viral proteins bearing bipartite, tryptophan‐based motifs have been shown to preferentially engage KLC2 (in addition to other light chain isoforms) to recruit kinesin‑1 for efficient anterograde transport of virions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In melanocytes, KLC2 partners with the adaptor SKIP to drive the microtubule‐dependent transport of melanosomes, illustrating a key mechanism by which the same motor machinery is tailored for the delivery of divergent cargoes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The importance of KLC2 is further underscored in epithelial cells, where its specific function is required for the microtubule‐dependent recruitment of Na⁺/K⁺‑ATPase–containing vesicles to the plasma membrane—a process critical for maintaining ion balance and cell polarity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In neurons, KLC2 directly interacts with LMTK2 to facilitate the axonal transport of regulatory complexes such as cdk5/p35, an association that may have repercussions for synaptic function and neurodegenerative processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, microRNA‐mediated regulation of KLC2—for instance, by miR‑125b in non‑small‐cell lung cancer—has been linked to enhanced cell migration and invasion, pointing to a proto‐oncogenic role for aberrant KLC2 expression in tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond these roles, KLC2 is indispensable for sensory cell function; studies in cochlear hair cells have demonstrated that loss of KLC2 disrupts mitochondrial distribution and synaptic integrity, leading to early‐onset low‑frequency hearing loss."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Structural investigations reveal that the tetratricopeptide repeat (TPR) domain of KLC2 exhibits notable plasticity, which underlies its capacity to bind a wide array of cargo adaptors with distinct molecular motifs."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In addition, proteomic approaches have positioned KLC2 within networks involved in Golgi–centrosomal organization, suggesting broader roles in maintaining cellular architecture and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Finally, silencing experiments indicate that KLC2 is critical for the anterograde transport of enveloped viral particles in neurons, further attesting to its central role in intracellular trafficking."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings identify KLC2 as a multifaceted cargo adaptor that not only governs the precise transport of vesicular and organellar cargoes but also integrates signaling, structural, and regulatory functions across diverse cell types. Its dynamic regulation by post‑translational modifications, its selective interaction with distinct cargo adaptors, and its involvement in key physiological processes—from synaptic transmission and sensory function to viral propagation and cancer cell behavior—highlight KLC2 as a potential target for therapeutic intervention in a broad spectrum of disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jing Du, Yanling Wei, Lidong Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A kinesin signaling complex mediates the ability of GSK-3beta to affect mood-associated behaviors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0913138107"}], "href": "https://doi.org/10.1073/pnas.0913138107"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20534517"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20534517"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Mark P Dodding, Richard Mitter, Ashley C Humphries, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A kinesin-1 binding motif in vaccinia virus that is widespread throughout the human genome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/emboj.2011.326"}], "href": "https://doi.org/10.1038/emboj.2011.326"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21915095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21915095"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Morié Ishida, Norihiko Ohbayashi, Mitsunori Fukuda "}, {"type": "b", "children": [{"type": "t", "text": "Rab1A regulates anterograde melanosome transport by recruiting kinesin-1 to melanosomes through interaction with SKIP."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep08238"}], "href": "https://doi.org/10.1038/srep08238"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25649263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25649263"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Humberto E Trejo, Emilia Lecuona, Doris Grillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of kinesin light chain-2 of kinesin-1 in the traffic of Na,K-ATPase-containing vesicles in alveolar epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.09-137802"}], "href": "https://doi.org/10.1096/fj.09-137802"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19773350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19773350"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Gábor M Mórotz, Elizabeth B Glennon, Patricia Gomez-Suaga, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LMTK2 binds to kinesin light chains to mediate anterograde axonal transport of cdk5/p35 and LMTK2 levels are reduced in Alzheimer's disease brains."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Acta Neuropathol Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s40478-019-0715-5"}], "href": "https://doi.org/10.1186/s40478-019-0715-5"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31068217"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31068217"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "M Wang, X Zhu, Z Sha, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High expression of kinesin light chain-2, a novel target of miR-125b, is associated with poor clinical outcome of elderly non-small-cell lung cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Br J Cancer (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/bjc.2015.3"}], "href": "https://doi.org/10.1038/bjc.2015.3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25668010"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25668010"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xiaolong Fu, Yachun An, Hongyang Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Deficiency of Klc2 Induces Low-Frequency Sensorineural Hearing Loss in C57BL/6 J Mice and Human."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Neurobiol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12035-021-02422-w"}], "href": "https://doi.org/10.1007/s12035-021-02422-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34014435"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34014435"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "The Quyen Nguyen, Mélanie Chenon, Fernando Vilela, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural plasticity of the N-terminal capping helix of the TPR domain of kinesin light chain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0186354"}], "href": "https://doi.org/10.1371/journal.pone.0186354"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29036226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29036226"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Silvio Alessandro Di Gioia, Pietro Farinelli, Stef J F Letteboer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interactome analysis reveals that FAM161A, deficient in recessive retinitis pigmentosa, is a component of the Golgi-centrosomal network."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddv085"}], "href": "https://doi.org/10.1093/hmg/ddv085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25749990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25749990"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Grayson DuRaine, Todd W Wisner, Paul Howard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kinesin-1 Proteins KIF5A, -5B, and -5C Promote Anterograde Transport of Herpes Simplex Virus Enveloped Virions in Axons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Virol (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/JVI.01269-18"}], "href": "https://doi.org/10.1128/JVI.01269-18"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30068641"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30068641"}]}]}]}