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The effects of pH on cortex and condensate formation. pH值对皮层和凝结物形成的影响。
IF 6.1 1区 生物学
Journal of Cell Biology Pub Date : 2026-12-07 Epub Date: 2026-10-16 DOI: 10.1083/jcb.202603108
Brooke E Waechtler, Chujun Liu, Bethany A Todd, Oiza Dimowo, Emma P Morin, Jasmine Barraza, Mashal Nawabi, Constance Campbell, Douglas N Robinson
{"title":"The effects of pH on cortex and condensate formation.","authors":"Brooke E Waechtler, Chujun Liu, Bethany A Todd, Oiza Dimowo, Emma P Morin, Jasmine Barraza, Mashal Nawabi, Constance Campbell, Douglas N Robinson","doi":"10.1083/jcb.202603108","DOIUrl":"10.1083/jcb.202603108","url":null,"abstract":"<p><p>The actin cortex enables cells to undergo shape changes in response to mechanical and chemical cues. Although F-actin and actin-associated proteins are present throughout cells, cortical structures assemble beneath the membrane, while actin-associated proteins form condensate-like structures in the cytoplasm. The mechanism regulating the separation between cortical and cytoplasmic phases remains unclear. Since many actin-associated proteins display pH-dependent interactions, intracellular pH gradients may contribute to this phase separation. Here, we investigate how pH regulates cortex assembly and condensate formation in Dictyostelium discoideum. We find that altering extracellular pH affects actin-associated protein's cortical localization and impacts their association with the actin network. Reconstitution assays indicate that cortexillin I-mediated actin crosslinking and bundling is enhanced at lower pH but can be affected by discoidin I, a weak, pH-dependent actin crosslinker. Finally, we found that the cell's cortical region is slightly more acidic than the cytoplasm, supporting a model in which intracellular pH helps regulate the balance between condensate assembly and cortex formation.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 12","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149206967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A nematode-trapping fungus orchestrates polarity cues, septins, and NOX signaling for trap formation. 线虫捕获真菌协调极性线索,sepins和氮氧化物信号的陷阱形成。
IF 6.1 1区 生物学
Journal of Cell Biology Pub Date : 2026-12-07 Epub Date: 2026-10-19 DOI: 10.1083/jcb.202603155
Chih-Yen Kuo, Hung-Che Lin, Yun-Zhen Chou, Sheng-An Chen, Hillel Schwartz, Yen-Ping Hsueh
{"title":"A nematode-trapping fungus orchestrates polarity cues, septins, and NOX signaling for trap formation.","authors":"Chih-Yen Kuo, Hung-Che Lin, Yun-Zhen Chou, Sheng-An Chen, Hillel Schwartz, Yen-Ping Hsueh","doi":"10.1083/jcb.202603155","DOIUrl":"10.1083/jcb.202603155","url":null,"abstract":"<p><p>Reprogramming cell morphogenesis in response to environmental cues is fundamental to microbial adaptation and survival. The nematode-trapping fungus (NTF) Arthrobotrys oligospora exemplifies this plasticity by developing adhesive traps to capture nematodes. However, mechanisms underlying trap morphogenesis and host invasion remain unclear. Using live-cell imaging, genetics, and functional assays, we show trap morphogenesis proceeds through localized redirection of hyphal growth followed by site-specific hyphal fusion, whereas infection development involves a transition from isotropic infection bulb expansion to multipolar invasive growth. These transitions are coordinated by the reorganization of conserved polarity proteins, asymmetric septin localization at the trap cell inner rim, and actin remodeling. Nematode-induced Nox1 signaling is required to recruit polarity and cytoskeletal machinery to the trap cell fusion site. Together, these findings establish NTF as a powerful model for understanding how conserved morphogenetic machinery drives the transition from linear hyphae to hyphal loops to trap nematodes.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 12","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Drosophila dendrites are resilient to adult-onset deficits in mitochondrial dynamics. 果蝇树突对线粒体动力学缺陷具有弹性。
IF 6.1 1区 生物学
Journal of Cell Biology Pub Date : 2026-12-07 Epub Date: 2026-10-19 DOI: 10.1083/jcb.202511010
Hailey Q Wang, Demetria G Fortson, Eavan D Burton, Hunter S Whitbeck, Briana M Robles, Kwass Wass, Letitia Bortey, Avi J Adler, Jordan I Kalai, Giovanna Napoleone, Erin L Barnhart
{"title":"Drosophila dendrites are resilient to adult-onset deficits in mitochondrial dynamics.","authors":"Hailey Q Wang, Demetria G Fortson, Eavan D Burton, Hunter S Whitbeck, Briana M Robles, Kwass Wass, Letitia Bortey, Avi J Adler, Jordan I Kalai, Giovanna Napoleone, Erin L Barnhart","doi":"10.1083/jcb.202511010","DOIUrl":"10.1083/jcb.202511010","url":null,"abstract":"<p><p>Mitochondrial transport, fusion, and fission are necessary for neuronal development, but the role of mitochondrial dynamics in neuronal maintenance remains unclear. In this work, we employed functional in vivo imaging of neurons in the Drosophila visual system, \"horizontal system\" (HS) cells, to determine how adult-onset deficits in mitochondrial dynamics affect mitochondrial localization, local regulation of ATP, and dendrite maintenance. In mature HS neurons, inhibition of mitochondrial transport or fusion depleted mitochondria from the dendrite over time but, surprisingly, had no effect on dendrite morphology. Moreover, adult-restricted mitochondrial mislocalization affected neither visual stimulus-driven dendritic calcium responses nor local, dynamic regulation of ATP levels. In contrast, when induced during development, the same perturbations caused mitochondrial mislocalization, loss of dendrite complexity, abrogation of stimulus-locked calcium responses and ATP fluctuations, and age-dependent dendrite degeneration. Thus, although mitochondrial dynamics are necessary during neuronal development, mature dendrites are capable of maintaining form and function in vivo upon mitochondrial depletion.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 12","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Biogenesis of nuclear lipid droplets is regulated by a Sir2-Csa1-Lro1 signaling pathway at the INM. 核脂滴的生物发生受INM的Sir2-Csa1-Lro1信号通路调控。
IF 6.1 1区 生物学
Journal of Cell Biology Pub Date : 2026-12-07 Epub Date: 2026-10-19 DOI: 10.1083/jcb.202506209
Lauren Carson, Hui Jin, Hong-Guo Yu
{"title":"Biogenesis of nuclear lipid droplets is regulated by a Sir2-Csa1-Lro1 signaling pathway at the INM.","authors":"Lauren Carson, Hui Jin, Hong-Guo Yu","doi":"10.1083/jcb.202506209","DOIUrl":"https://doi.org/10.1083/jcb.202506209","url":null,"abstract":"<p><p>In response to cellular signals, lipid droplets are formed at the inner nuclear membrane (INM), which plays a key role in maintaining membrane homeostasis and energy storage. However, the signaling pathway that regulates nuclear lipid droplet biogenesis remains to be elucidated. Here, we show that in budding yeast, the INM-localized protein Csa1 regulates the localization of the acyltransferase Lro1, which converts diacylglycerol to triacylglycerol, leading to nuclear lipid droplet synthesis. Csa1 possesses two nuclear localization signals, along with an amphipathic helix that anchors it to the INM. Upon nutrient depletion, both Csa1 and Lro1 are enriched at a distinct INM subdomain that abuts the nucleolus, which we term the n-INM. Csa1 interacts with the ubiquitin-conjugating enzyme Ubc4 and protects nuclear Lro1 from degradation by the proteasome. Furthermore, the deacetylase activity of Sir2 is required for the n-INM enrichment of both Csa1 and Lro1. Our findings uncover an unexpected Sir2-Csa1-Lro1 signaling pathway at the INM that regulates nuclear membrane homeostasis.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 12","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
ARF-1 coordinates cargo sorting at FERARI endosomal recycling hubs. ARF-1协调FERARI内体回收中心的货物分类。
IF 6.1 1区 生物学
Journal of Cell Biology Pub Date : 2026-12-07 Epub Date: 2026-10-19 DOI: 10.1083/jcb.202512157
Jachen A Solinger, Curdin A Franziscus, Trian Nuredini, Dominic L Müller, Staf Clement, Danilo Ritz, Petia Adarska, Francesca Bottanelli, Anne Spang
{"title":"ARF-1 coordinates cargo sorting at FERARI endosomal recycling hubs.","authors":"Jachen A Solinger, Curdin A Franziscus, Trian Nuredini, Dominic L Müller, Staf Clement, Danilo Ritz, Petia Adarska, Francesca Bottanelli, Anne Spang","doi":"10.1083/jcb.202512157","DOIUrl":"https://doi.org/10.1083/jcb.202512157","url":null,"abstract":"<p><p>Endosomal pathways are central to cellular organization, compartmentalization, and intercellular communication. Independent of the endocytic entry route, sorting endosomes function as critical junctions at which membrane proteins are sorted for recycling or degradation. The multicomponent tether FERARI orchestrates recycling by coordinating Rab GTPase activity with vesicle fusion and fission through a kiss-and-run (KAR) mechanism. Here, we identify the small GTPase ARF-1 as an essential regulator of cargo loading at FERARI-dependent endosomal KAR sites. Cycling of ARF-1 between its active and inactive states is required for efficient cargo capture into recycling vesicles. Our findings support a model in which cycling ARF-1 activity governs the temporal association of cargo with adaptor proteins and complexes, thereby controlling selective uptake into vesicles destined for the plasma membrane. These results uncover a previously unappreciated layer of regulation of endosomal recycling and highlight the interplay between ARF and Rab family GTPases in this process.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 12","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Single-cell imaging reveals a key role of Bck2 in yeast cell size adaptation to nutrient challenges. 单细胞成像揭示了Bck2在酵母细胞大小适应营养挑战中的关键作用。
IF 6.1 1区 生物学
Journal of Cell Biology Pub Date : 2026-12-07 Epub Date: 2026-10-09 DOI: 10.1083/jcb.202410020
Yagya Chadha, Igor V Kukhtevich, Timon Stegmaier, Francesco Padovani, Robert Schneider, Kurt M Schmoller
{"title":"Single-cell imaging reveals a key role of Bck2 in yeast cell size adaptation to nutrient challenges.","authors":"Yagya Chadha, Igor V Kukhtevich, Timon Stegmaier, Francesco Padovani, Robert Schneider, Kurt M Schmoller","doi":"10.1083/jcb.202410020","DOIUrl":"10.1083/jcb.202410020","url":null,"abstract":"<p><p>Cell size is tightly controlled to optimize cell function. In Saccharomyces cerevisiae, multiple regulators of cell size in steady-state conditions have been identified, such as the G1/S activators Cln3 and Bck2 and the inhibitor Whi5. Individual deletions of these regulators alter the mean cell volumes. However, size homeostasis remains largely intact. Here, we show that although the roles of Bck2 and Cln3 for cell size regulation appear largely redundant in steady state, a switch from fermentable to nonfermentable growth media reveals a unique role for Bck2 in cell size adaptation. We use live-cell microscopy and machine learning-assisted image analysis to track single cells and their progeny through the nutrient switch. We find that after the switch, bck2Δ cells experience longer cell cycle arrests and more arrest-associated enlargement than wild-type, whi5Δ, or cln3Δ cells, indicating that Bck2 becomes the critical G1/S activator in changing nutrients. Our work demonstrates that studying size regulation during nutrient shifts can resolve apparent redundancies observed in steady state.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 12","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13651637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149136825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microtubules and nuclear pores position centromeres and genes in neural stem cells. 在神经干细胞中,微管和核孔定位着丝粒和基因。
IF 6.1 1区 生物学
Journal of Cell Biology Pub Date : 2026-12-07 Epub Date: 2026-10-14 DOI: 10.1083/jcb.202512057
Jennifer A Taylor, Clemens Cabernard
{"title":"Microtubules and nuclear pores position centromeres and genes in neural stem cells.","authors":"Jennifer A Taylor, Clemens Cabernard","doi":"10.1083/jcb.202512057","DOIUrl":"https://doi.org/10.1083/jcb.202512057","url":null,"abstract":"<p><p>Chromatin's spatial organization is important for cell division, epigenetic memory, and gene regulation. Chromatin architecture is often reflected in nonrandom centromere positioning, which changes during development and disease. However, the mechanisms and functions of centromere positioning remain largely unknown. Here, we report that Drosophila neural stem cells cluster centromeres near the nuclear envelope, adjacent to the apical centrosome. This asymmetric centromere positioning persists throughout interphase but is lost in differentiated progeny. Asymmetric centromere positioning is regulated by microtubules from the apical centrosome connected to nuclear pore complexes (NPCs), generating a pulling force mediated by the motor protein Dynein and its binding partner Mushroom body defect. Lamin facilitates centromere-NPC binding, necessary for centromere positioning and clustering. We also find that the developmentally regulated genes hunchback and pendulin occupy specific nuclear regions, correlating with polarized centromere localization. We propose that fly neural stem cells translate their inherent polarity into stereotypical chromatin organization, potentially influencing cell-fate decisions and stem cell behavior.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 12","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MapZ phosphorylation drives EzrA recruitment to the future division site of Streptococcus pneumoniae. MapZ磷酸化驱动以斯拉招募到肺炎链球菌的未来分裂位点。
IF 6.1 1区 生物学
Journal of Cell Biology Pub Date : 2026-12-07 Epub Date: 2026-10-14 DOI: 10.1083/jcb.202601063
Cassandra Lenoir, Hugo Millat, Cassandra Falcou, Céline Freton, Jean-Pierre Lavergne, Cécile Morlot, Thomas G Bernhardt, Adrien Ducret, Christophe Grangeasse
{"title":"MapZ phosphorylation drives EzrA recruitment to the future division site of Streptococcus pneumoniae.","authors":"Cassandra Lenoir, Hugo Millat, Cassandra Falcou, Céline Freton, Jean-Pierre Lavergne, Cécile Morlot, Thomas G Bernhardt, Adrien Ducret, Christophe Grangeasse","doi":"10.1083/jcb.202601063","DOIUrl":"https://doi.org/10.1083/jcb.202601063","url":null,"abstract":"<p><p>MapZ dictates the positioning of FtsZ that organizes the assembly of the cell division machinery (divisome) at the midcell in Streptococcus pneumoniae. While the molecular mechanisms by which MapZ localizes to and drives the divisome at the midcell are well characterized, the role of its phosphorylation by the serine/threonine kinase StkP remains enigmatic. Here, we provide evidence that MapZ interacts with the cell division protein EzrA. We further demonstrate that this interaction is modulated by the phosphorylation of MapZ. We also show that MapZ phosphorylation influences the localization and dynamics of EzrA. We examined the localization of MapZ, EzrA, and StkP using fluorescent fusion proteins in pairwise and triplewise combinations and revealed that these proteins exhibit distinct dynamics at the division septum. Our observations support a model in which MapZ phosphorylation fine-tunes the localization and dynamics of EzrA, thereby ensuring proper cell division.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 12","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Nucleolar dynamics are determined by the ordered assembly of the ribosome. 核仁动力学是由核糖体有序组装决定的。
IF 6.1 1区 生物学
Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-09-09 DOI: 10.1083/jcb.202605096
Jessica Sheu-Gruttadauria, Xiaowei Yan, Nico Stuurman, Riley O Ogrean, Sabrina Lin, Stephen N Floor, Ronald D Vale
{"title":"Nucleolar dynamics are determined by the ordered assembly of the ribosome.","authors":"Jessica Sheu-Gruttadauria, Xiaowei Yan, Nico Stuurman, Riley O Ogrean, Sabrina Lin, Stephen N Floor, Ronald D Vale","doi":"10.1083/jcb.202605096","DOIUrl":"10.1083/jcb.202605096","url":null,"abstract":"<p><p>Ribosome biogenesis occurs in the nucleolus, a biomolecular condensate whose material properties are thought to be important for function. However, the molecular basis of nucleolar dynamics and their relationship to ribosome assembly remain incompletely understood. We present a platform for high-throughput FRAP (HiT-FRAP) and use it to screen hundreds of genes for their impact on dynamics of the nucleolar scaffold nucleophosmin (NPM1). We find that NPM1 dynamics and nucleolar morphology are sensitive to ribosome assembly state: accumulation of early pre-ribosomal intermediates slows NPM1 dynamics and compacts the condensate, while accumulation of abortive late precursors accelerates dynamics and disrupts condensate integrity. These opposing biophysical states correlate with the strength of NPM1-pre-ribosome interactions. Importantly, mutations in the NPM1 intrinsically disordered region that alter pre-ribosome binding directly tune nucleolar dynamics. These results establish that ribosomal precursor assembly state determines nucleolar material properties through the strength of scaffold-pre-ribosome interactions and introduce HiT-FRAP as a platform for interrogating condensate dynamics broadly.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 11","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Pathogenic KIF1A variants differentially disrupt axonal trafficking and impede synaptic development. 致病性KIF1A变异破坏轴突运输并阻碍突触发育。
IF 6.1 1区 生物学
Journal of Cell Biology Pub Date : 2026-11-02 Epub Date: 2026-09-07 DOI: 10.1083/jcb.202601034
Jayne Aiken, Carris Borland, Nicolas Marotta, Benjamin L Prosser, Erika L F Holzbaur
{"title":"Pathogenic KIF1A variants differentially disrupt axonal trafficking and impede synaptic development.","authors":"Jayne Aiken, Carris Borland, Nicolas Marotta, Benjamin L Prosser, Erika L F Holzbaur","doi":"10.1083/jcb.202601034","DOIUrl":"10.1083/jcb.202601034","url":null,"abstract":"<p><p>The nervous system relies on billions of neurons connected through trillions of synapses to support vital functions. Despite the importance of this synaptic network, cellular mechanisms dictating synapse formation during human neurodevelopment remain unclear. Long-distance trafficking by the microtubule motor KIF1A is crucial for synaptogenesis and downstream synapse maintenance. Mutations in KIF1A cause KIF1A-associated neurological disorder (KAND). We employed isogenic gene-edited human-induced pluripotent stem cell -derived neurons to assess the effects of disparate pathogenic mutations in KIF1A on synaptic trafficking and function. Null (p.C92*) and hypoactive (p.P305L) mutations delay neurite outgrowth, mislocalize synaptic cargoes, and decrease synapse density. Conversely, a hyperactive (p.R350G) mutation supports neurite outgrowth but causes aberrant motility of synaptic vesicle precursors and deficits in microtubule-dependent presynaptic patterning. Functional analysis of neuronal activity reveals delayed synaptic maturation in loss-of-function mutations (p.P305L, p.C92*) and precocious activity in the hyperactive p.R350G mutation. These data provide insights into how KIF1A mutations with distinct molecular-level impacts lead to significant downstream synaptic deficits in human neurons.</p>","PeriodicalId":15211,"journal":{"name":"Journal of Cell Biology","volume":"225 11","pages":""},"PeriodicalIF":6.1,"publicationDate":"2026-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13552237/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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