{"title":"Heterodimeric Ciliary Dynein f/I1 Adopts a Distinctive Structure, Providing Insight Into the Autoinhibitory Mechanism Common to the Dynein Family.","authors":"Yici Lei, Akira Fukunaga, Hiroshi Imai, Ryosuke Yamamoto, Rieko Shimo-Kon, Shinji Kamimura, Kaoru Mitsuoka, Takako Kato-Minoura, Toshiki Yagi, Takahide Kon","doi":"10.1002/cm.21987","DOIUrl":"https://doi.org/10.1002/cm.21987","url":null,"abstract":"<p><p>Dyneins are huge motor protein complexes that are essential for cell motility, cell division, and intracellular transport. Dyneins are classified into three major subfamilies, namely cytoplasmic, intraflagellar-transport (IFT), and ciliary dyneins, based on their intracellular localization and functions. Recently, several near-atomic resolution structures have been reported for cytoplasmic/IFT dyneins. In contrast, the structures of ciliary dyneins, as well as their regulatory mechanisms, have yet to be fully elucidated. Here, we isolated a heterodimeric ciliary dynein (IDA-f/I1) from Chlamydomonas reinhardtii, a ciliated green alga, and studied its structure in the presence or absence of ATP by negative-stain electron microscopy and single-particle analysis. Surprisingly, a population of IDA-f adopted a distinctive compact structure, which has been scarcely reported for ciliary dyneins but is very similar to the \"phi-particle\" structure widely recognized as the autoinhibited/inactivated conformation for cytoplasmic/IFT dyneins. Our results suggest that the inactivation mechanism of dimeric dyneins is conserved in all three dynein subfamilies, regardless of their cellular functions, highlighting the intriguing intrinsic regulatory mechanism that may have been acquired at an early stage in the evolution of dynein motors.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maria Giovanna Riparbelli, Massimo Migliorini, Giuliano Callaini
{"title":"Astral Microtubules Are Dispensable for Pavarotti Localization During Drosophila Spermatogonial Mitoses.","authors":"Maria Giovanna Riparbelli, Massimo Migliorini, Giuliano Callaini","doi":"10.1002/cm.21986","DOIUrl":"https://doi.org/10.1002/cm.21986","url":null,"abstract":"<p><p>We analysed here the dynamic of the kinesin-like Pavarotti (Pav) during male gametogenesis of wild-type and Sas4 mutant flies. Pav localizes to the equatorial region and the inner central spindle of late anaphase wild-type spermatogonia and displays a strong concentration at the midbody during late telophase. At metaphase of the first meiotic division, Pav shows widespread localization on the equatorial region of the spermatocytes. This unusual distribution restricts and enhances during anaphase where antiparallel cortical microtubules overlap. Additional Pav staining is also found in the inner central spindle where the microtubules overlap between the segregating chromosomes. At late telophase, Pav accumulates to the midbody and on a weak ring that surround the cytoplasmic bridges. Pav localizes in an equatorial discontinuous ring of Sas4 spermatogonia where the non-centrosomal microtubules overlap, but the motor protein is absent in the interior central spindle where the inner microtubules are lacking. However, the anastral spindles properly support cell division, suggesting that astral microtubules are dispensable for Pav localization in the Sas4 spermatogonial cell cortex. This function is presumably replaced by the antiparallel cortical microtubules extending from the acentriolar polar regions. In contrast, the majority of the meiotic spindles in Sas4 mutant testes do not progress beyond late anaphase, and only a small fraction of the primary spermatocytes experienced an abnormal division with the assembly of aberrant telophase spindles. Pav accumulates around the chromatin clusters or enhanced at the plus ends of the antiparallel non-centrosomal cortical bundles of microtubules. However, these bundles are not arranged properly in the equatorial region of the cell and cytokinesis is abnormal or fails. Therefore, the observations in Sas4 mutant testes suggest that the spermatogonial mitoses correctly occur in the absence of astral microtubules, whereas meiotic divisions fail.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142928763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tubules, Rods, and Spirals: Diverse Modes of SepF-FtsZ Assembling.","authors":"Jagrity Choudhury, Barnali N Chaudhuri","doi":"10.1002/cm.21975","DOIUrl":"https://doi.org/10.1002/cm.21975","url":null,"abstract":"<p><p>Z-ring formation by FtsZ, the master assembler of the divisome, is a key step in bacterial cell division. Membrane anchoring of the Z-ring requires the assistance of dedicated Z-ring binding proteins, such as SepF and FtsA. SepF participates in bundling and membrane anchoring of FtsZ in gram-positive bacteria. We report in vitro biophysical studies of the interactions between FtsZ and a cytoplasmic component of cognate SepF from three different bacteria: Mycobacterium tuberculosis, Staphylococcus aureus, and Enterococcus gallinarum. While the cytosolic domain of SepF from M. tuberculosis is primarily a dimer, those from S. aureus and E. gallinarum polymerize to form ring-like structures. Mycobacterial SepF helps in the bundling of FtsZ filaments to form thick filaments and large spirals. On the other hand, ring-forming SepF from the Firmicutes bundle FtsZ into tubules. Our results suggest that the oligomeric form of SepF directs how it bundles FtsZ filaments.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"End Binding Proteins: Drivers of Cancer Progression.","authors":"Dhakshmi Sasankan, Renu Mohan","doi":"10.1002/cm.21972","DOIUrl":"https://doi.org/10.1002/cm.21972","url":null,"abstract":"<p><p>Cancer, a complex and heterogeneous disease, continues to be a major global health concern. Despite advancements in diagnostics and therapeutics, the aggressive nature of certain cancers remain a significant challenge, necessitating a deeper understanding of the underlying molecular mechanisms driving their severity and progression. Cancer severity and progression depend on cellular properties such as cell migration, cell division, cell shape changes, and intracellular transport, all of which are driven by dynamic cellular microtubules. Dynamic properties of microtubules, in turn, are regulated by an array of proteins that influence their stability and growth. Among these regulators, End Binding (EB) proteins stand out as critical orchestrators of microtubule dynamics at their growing plus ends. Beyond their fundamental role in normal cellular functions, recent research has uncovered compelling evidence linking EB proteins to the pathogenesis of various diseases, including cancer progression. As the field of cancer research advances, the clinical implication of EB proteins role in cancer severity and aggressiveness become increasingly evident. This review aims to comprehensively explore the role of microtubule-associated EB proteins in influencing the severity and aggressiveness of cancer. We also discuss the potential significance of EB as a clinical biomarker for cancer diagnosis and prognosis and as a target for therapeutic intervention.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Overexpressed Palladin Rescues Enteropathogenic E. coli (EPEC) Pedestal Lengths in ArpC2 Depleted Cells.","authors":"Kaitlin M Bruzzini, S Tara Mann, Julian A Guttman","doi":"10.1002/cm.21974","DOIUrl":"https://doi.org/10.1002/cm.21974","url":null,"abstract":"<p><p>Enteropathogenic Escherichia coli (EPEC) causes diarrheal disease. Once ingested, these extracellular pathogens attach to the intestinal epithelial cells of their host, collapse the localized microvilli, and generate actin-rich structures within the host cells that are located beneath the attached bacteria, called \"pedestals.\" Palladin is an actin-associated protein that cross-links and stabilizes actin filaments. This protein also acts as a scaffolding protein for other actin-binding proteins. Here, we examine the role of Palladin during EPEC infections and show that Palladin is co-opted by EPEC. Depletion of Palladin resulted in shorter pedestals, and when Palladin containing mutations in either its actin- or VASP-binding domains were overexpressed in cells, pedestals decreased in length. Importantly, we show that the overexpression of Palladin in ArpC2<sup>-/-</sup> (Arp2/3 complex-depleted) cells rescued pedestal length. Together, our results demonstrate that Palladin has the ability to rescue pedestal length during EPEC infections when the function of the Arp2/3 complex is diminished.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Conformational Regulation of Vertebrate γ-Tubulin Ring Complexes by CM1 Proteins.","authors":"Michal Wieczorek","doi":"10.1002/cm.21979","DOIUrl":"https://doi.org/10.1002/cm.21979","url":null,"abstract":"","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Osteocyte Dendrites: How Do They Grow, Mature, and Degenerate in Mineralized Bone?","authors":"Rosa M Guerra, Velia M Fowler, Liyun Wang","doi":"10.1002/cm.21964","DOIUrl":"https://doi.org/10.1002/cm.21964","url":null,"abstract":"<p><p>Osteocytes, the most abundant bone cells, form an extensive cellular network via interconnecting dendrites. Like neurons in the brain, the long-lived osteocytes perceive mechanical and biological inputs and signal to other effector cells, leading to the homeostasis and turnover of bone tissues. Despite the appreciation of osteocytes' vital roles in bone biology, the initiation, growth, maintenance, and eventual degradation of osteocyte dendrites are poorly understood due to their full encasement by mineralized matrix. With the advancement of imaging modalities and genetic models, the architectural organization and molecular composition of the osteocyte dendrites, as well as their morphological changes with aging and diseases, have begun to be revealed. However, several long-standing mysteries remain unsolved, including (1) how the dendrites are initiated and elongated when a surface osteoblast becomes embedded as an osteocyte; (2) how the dendrites maintain a relatively stable morphology during their decades-long life span; (3) what biological processes control the dendrite morphology, connectivity, and stability; and (4) if these processes are influenced by age, sex, hormones, and mechanical loading. Our review of long, thin actin filament (F-actin)-containing processes extending from other cells leads to a working model that serves as a starting point to investigate the formation and maintenance of osteocyte dendrites and their degradation with aging and diseases.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142803765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unjamming Transition as a Paradigm for Biomechanical Control of Cancer Metastasis.","authors":"Grace Cai, Nicole C Rodgers, Allen P Liu","doi":"10.1002/cm.21963","DOIUrl":"https://doi.org/10.1002/cm.21963","url":null,"abstract":"<p><p>Tumor metastasis is a complex phenomenon that poses significant challenges to current cancer therapeutics. While the biochemical signaling involved in promoting motile phenotypes is well understood, the role of biomechanical interactions has recently begun to be incorporated into models of tumor cell migration. Specifically, we propose the unjamming transition, adapted from physical paradigms describing the behavior of granular materials, to better discern the transition toward an invasive phenotype. In this review, we introduce the jamming transition broadly and narrow our discussion to the different modes of 3D tumor cell migration that arise. Then we discuss the mechanical interactions between tumor cells and their neighbors, along with the interactions between tumor cells and the surrounding extracellular matrix. We center our discussion on the interactions that induce a motile state or unjamming transition in these contexts. By considering the interplay between biochemical and biomechanical signaling in tumor cell migration, we can advance our understanding of biomechanical control in cancer metastasis.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}