Ask about this productRelated genes to: KIF1A antibody
- Gene:
- KIF1A NIH gene
- Name:
- kinesin family member 1A
- Previous symbol:
- ATSV, C2orf20, SPG30
- Synonyms:
- UNC104
- Chromosome:
- 2q37.3
- Locus Type:
- gene with protein product
- Date approved:
- 1995-12-18
- Date modifiied:
- 2019-04-23
Related products to: KIF1A antibody
Related articles to: KIF1A antibody
- The kinesin-3 family member, KIF1A is an essential motor protein that carries out intracellular transport in neurons. Previous work has established that: 1) intracellular transport can be impaired in neurodegenerative diseases such as Alzheimer's and Parkinson's; and 2) oxidative stress is elevated in neurodegenerative diseases and during aging. To date there has not been a systematic study of the effects of reactive oxygen species on kinesin motor proteins. We hypothesized that oxidative stress can damage kinesin, leading to decreased motility. To test our hypothesis, we treated KIF1A in vitro with varying concentrations of hydrogen peroxide (HO), a common reactive oxygen species, and characterized the impacts on KIF1A function. Pretreatment of KIF1A with HO at concentrations of 1 mM and higher decreased motility in microtubule gliding assays. In single-molecule assays KIF1A was impacted in two ways: a fraction of motors moved with slowed velocity, while a fraction of motors moved only diffusively with no net directionality. Non-reducing SDS-PAGE of oxidized kinesin showed higher molecular weight bands, consistent with disulfide-bonded dimers and higher-order species. Treating oxidized motors with reducing agents reversed this crosslinking and partially restored motility. Replacing cysteine residues in the motor domain reduced the effects of moderate oxidation but did not prevent the severe degradation of motility at the highest HO concentrations, indicating there is irreversible oxidative damage beyond only cysteine residues. Our results suggest that KIF1A can be impacted by oxidative stress and raise the possibility that oxidized KIF1A may be involved in the pathogenesis of neurodegenerative diseases. - Source: PubMed
Publication date: 2026/04/17
Chen Adrien PPandey HimanshuHancock William O - Programmed death-ligand 1 (PD-L1) expression is routinely used to guide immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (NSCLC), yet clinical benefit remains heterogeneous even among PD-L1-high tumors. Liquid biopsy based on cell-free DNA (cfDNA) enables minimally invasive, real-time monitoring of tumor evolution. We report four cases of metastatic lung adenocarcinoma treated with atezolizumab, integrating longitudinal whole-exome sequencing (WES) of cfDNA with radiological assessment. Four patients with PD-L1-positive (≥60%) metastatic NSCLC received atezolizumab monotherapy. Serial cfDNA samples (1-3 per patient) were analyzed by high-depth WES. Distinct molecular trajectories paralleled divergent clinical outcomes. One patient achieved a complete molecular response, characterized by progressive clearance of , , and mutant clones, which was concordant with radiological remission. A second patient showed an initial molecular response, followed by clonal rebound of , , and mutant populations and the emergence of and variants, suggesting clinical progression. Two patients exhibited primary resistance despite high PD-L1 expression, with persistent or expanding clones and early subclonal diversification; in one case, new and alterations emerged under treatment pressure. Notably, switching to platinum-based chemotherapy in a non-responder induced a measurable molecular response, highlighting discordance between PD-L1 status and immunotherapy efficacy. Longitudinal cfDNA WES captured dynamic clonal remodeling under immunotherapy and anticipated radiological outcomes. These findings underscore the clinical necessity of integrating dynamic molecular monitoring by liquid biopsy to overcome the limitations of static PD-L1 assessment, refine therapeutic stratification, and identify early resistance mechanisms in advanced NSCLC. - Source: PubMed
Publication date: 2026/03/24
Serio Viola BiancaRegoli TommasoMaffeo DeboraMartellucci IgnazioRosati DilettaGhisalberti MarcoBalistreri AlbertoSantamaria GianlucaVono NiccolòMari FrancescaColombo FrancescaFrullanti ElisaPalmieri Maria - Elucidating the pathophysiological mechanisms of mental disorders remains a critical challenge in psychiatric research. Recent studies have highlighted the potential involvement of cytoskeletal and molecular motor abnormalities in the development of mental disorders such as schizophrenia and autism spectrum disorder (ASD). Although schizophrenia and ASD differ clinically, both disorders are increasingly regarded as neurodevelopmental conditions and share vulnerabilities in synapse formation and neural circuit maturation. This review synthesizes the latest findings on the relationship between cytoskeletal and molecular motor abnormalities and mental disorders. The cytoskeleton, composed of microtubules, actin filaments, and intermediate filaments, along with molecular motors such as kinesins, dyneins, and myosins, plays crucial roles in neurodevelopment, synapse formation, and neurotransmission. In schizophrenia, decreased expression of the microtubule-associated protein MAP2 and abnormalities in the DISC1 gene have been reported, potentially leading to dendritic morphological abnormalities and neurodevelopmental disorders. Additionally, abnormalities in molecular motors such as KIF17 and KIF1A have been implicated in schizophrenia pathophysiology. Myosin Id has been identified as a risk gene for ASD. Furthermore, abnormalities in actin-related proteins such as SHANK3 and CYFIP1 have been shown to cause synaptic dysfunction. These findings suggest that mental disorders arise from complex pathologies involving multiple cytoskeletal and molecular motor-related protein abnormalities. Future research should focus on elucidating the functions of individual proteins and adopting a comprehensive approach that includes glial cells. Advances in this field may deepen our understanding of the pathophysiological mechanisms of mental disorders and potentially lead to the development of novel therapeutic strategies. - Source: PubMed
Publication date: 2026/03/30
Nakamura KenyuKubo AsumiSanaka SaeKamiya SaraItagaki KentaroSasaki Tetsuya
- Source: PubMed
- Pathogenic variants in the motor domain of the kinesin-3 motor protein KIF1A cause a range of neurodevelopmental and neurodegenerative conditions collectively termed KIF1A-associated neurological disorder (KAND). Among these, mutations at residue R350 are linked to hereditary spastic paraplegia and altered motor function. Yet, the structural basis for their pathogenicity remains unclear. Here, we present high-resolution cryo-electron microscopy (cryo-EM) structures of KIF1A R350G and R350W bound to microtubules in both the apo and AMP-PNP-bound states. We identify a salt bridge between KIF1A residue R350 and α-tubulin E415 that forms only in the open conformation of the motor domain and is disrupted in both mutants. The loss of this electrostatic interaction correlates with increased velocity, reduced processivity, and decreased microtubule affinity in the open, apo conformation, as demonstrated by single-molecule assays. Our results reveal an electrostatic interaction at the motor-microtubule interface that regulates KIF1A's motility behavior. - Source: PubMed
Publication date: 2026/03/31
Shatarupa AbhipsaRao LuAsenjo Ana BGennerich ArneSosa Hernando