This review examines the diverse functions of dyneins, a family of motor proteins involved in intracellular transport processes, the maintenance of cell polarity, and critical signaling pathways essential for cell cycle progression. Dyneins' significant impact on critical cellular functions is mediated through their interactions with an array of organelles, including centrosomes, chromosomes, and endosomes. Dyneins also influence autophagy and immune evasion within the complex environment of cancer. This review underscores the significance of dyneins as an avenue of exploration for comprehending the intricate mechanisms that underpin cancer.
{"title":"Dynein: A Multifaceted Therapeutic Target and Its Dysregulation in Aberrant Cell Proliferation.","authors":"Jivesh Garg, Laleh Alisaraie","doi":"10.1002/cm.22041","DOIUrl":"https://doi.org/10.1002/cm.22041","url":null,"abstract":"<p><p>This review examines the diverse functions of dyneins, a family of motor proteins involved in intracellular transport processes, the maintenance of cell polarity, and critical signaling pathways essential for cell cycle progression. Dyneins' significant impact on critical cellular functions is mediated through their interactions with an array of organelles, including centrosomes, chromosomes, and endosomes. Dyneins also influence autophagy and immune evasion within the complex environment of cancer. This review underscores the significance of dyneins as an avenue of exploration for comprehending the intricate mechanisms that underpin cancer.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144722","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}
The dynamic interaction between actin filaments (AFs) and microtubules (MTs) plays a crucial role in regulating key developmental and physiological processes in plant cells, particularly in the formation of specialized cell types with distinct shapes and functions, such as pollen tubes, trichomes, and leaf epidermal cells. These cytoskeletal components are organized into specialized structures, and their coordination is tightly regulated by molecular mechanisms, including ROP signaling pathways that control actin- and microtubule-binding proteins. Additionally, bifunctional proteins such as kinesins and myosins, which interact with both AFs and MTs, further facilitate the coordination of cytoskeletal activities, thus regulating cell morphology. Recent advances in understanding of stomatal development (Arabidopsis and maize), moss protonemal cells, and xylem differentiation have provided novel mechanistic insights into cytoskeletal crosstalk. This review, based on recent discoveries, focuses on the role of actin-microtubule interactions in the formation of new cell types, vesicular transport, and cell division. Furthermore, we highlight the molecular mechanisms that govern these interactions and propose future research directions in this field.
{"title":"Interaction Between Actin and Microtubules During Plant Development.","authors":"Zining Wu, Lidong Gao, M Arif Ashraf, Qiong Nan","doi":"10.1002/cm.22029","DOIUrl":"https://doi.org/10.1002/cm.22029","url":null,"abstract":"<p><p>The dynamic interaction between actin filaments (AFs) and microtubules (MTs) plays a crucial role in regulating key developmental and physiological processes in plant cells, particularly in the formation of specialized cell types with distinct shapes and functions, such as pollen tubes, trichomes, and leaf epidermal cells. These cytoskeletal components are organized into specialized structures, and their coordination is tightly regulated by molecular mechanisms, including ROP signaling pathways that control actin- and microtubule-binding proteins. Additionally, bifunctional proteins such as kinesins and myosins, which interact with both AFs and MTs, further facilitate the coordination of cytoskeletal activities, thus regulating cell morphology. Recent advances in understanding of stomatal development (Arabidopsis and maize), moss protonemal cells, and xylem differentiation have provided novel mechanistic insights into cytoskeletal crosstalk. This review, based on recent discoveries, focuses on the role of actin-microtubule interactions in the formation of new cell types, vesicular transport, and cell division. Furthermore, we highlight the molecular mechanisms that govern these interactions and propose future research directions in this field.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059700","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}
The plant cell wall, a rigid structural layer that surrounds each plant cell, is critical for regulating and controlling cell growth. Microtubules play a role in the production of cell walls by regulating the transport and deposition of cell wall components in a spatial and temporal manner. The dynamic behavior of microtubules and their anchoring to the plasma membrane are factors that contribute to the achievement of production of the cell wall and growth of the cell. This mini review provides an overview of the plant cell wall and its dynamic interactions with microtubules. It emphasizes the role of specific proteins that mediate these interactions, supported by experimental evidence from mutant studies.
{"title":"Cell Wall-Microtubule Interactions in Plant Cell.","authors":"Arpita Yadav","doi":"10.1002/cm.22027","DOIUrl":"https://doi.org/10.1002/cm.22027","url":null,"abstract":"<p><p>The plant cell wall, a rigid structural layer that surrounds each plant cell, is critical for regulating and controlling cell growth. Microtubules play a role in the production of cell walls by regulating the transport and deposition of cell wall components in a spatial and temporal manner. The dynamic behavior of microtubules and their anchoring to the plasma membrane are factors that contribute to the achievement of production of the cell wall and growth of the cell. This mini review provides an overview of the plant cell wall and its dynamic interactions with microtubules. It emphasizes the role of specific proteins that mediate these interactions, supported by experimental evidence from mutant studies.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144051555","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}
Zihan Yin, Yirong Gan, Yin Chen, Elena Kozgunova, Peishan Yi
Microtubules (MTs) are essential cytoskeletal elements in all eukaryotes, playing critical roles in cell shape, intercellular organization, cell division, and cell motility. The organization of the MT network has undergone significant changes throughout plant evolution. Some MT structures, such as the preprophase band and phragmoplast, are innovations in plant lineages, while others, including the centriole and flagellum, have been lost over time. Bryophytes, consisting of mosses, liverworts, and hornworts, are the earliest land plants and occupy a key phylogenetic position in the evolution of MT organization. In the past two decades, advances in genomics, genetics, and cell imaging technologies have significantly enhanced our understanding of MT organization and function. Two representative species, Physcomitrium patens (moss) and Marchantia polymorph (liverwort), have become established model organisms, and new models for hornworts are emerging. In this review, we summarize the current knowledge of the MT cytoskeleton, drawing from early electron microscopy studies and recent advances in these emerging models. Our aim is to provide a comprehensive overview of the major MT array types and key factors involved in MT organization in bryophytes, offering insights into MT adaptation during plant evolution.
{"title":"The Microtubule Cytoskeleton in Bryophytes.","authors":"Zihan Yin, Yirong Gan, Yin Chen, Elena Kozgunova, Peishan Yi","doi":"10.1002/cm.22009","DOIUrl":"https://doi.org/10.1002/cm.22009","url":null,"abstract":"<p><p>Microtubules (MTs) are essential cytoskeletal elements in all eukaryotes, playing critical roles in cell shape, intercellular organization, cell division, and cell motility. The organization of the MT network has undergone significant changes throughout plant evolution. Some MT structures, such as the preprophase band and phragmoplast, are innovations in plant lineages, while others, including the centriole and flagellum, have been lost over time. Bryophytes, consisting of mosses, liverworts, and hornworts, are the earliest land plants and occupy a key phylogenetic position in the evolution of MT organization. In the past two decades, advances in genomics, genetics, and cell imaging technologies have significantly enhanced our understanding of MT organization and function. Two representative species, Physcomitrium patens (moss) and Marchantia polymorph (liverwort), have become established model organisms, and new models for hornworts are emerging. In this review, we summarize the current knowledge of the MT cytoskeleton, drawing from early electron microscopy studies and recent advances in these emerging models. Our aim is to provide a comprehensive overview of the major MT array types and key factors involved in MT organization in bryophytes, offering insights into MT adaptation during plant evolution.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560265","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}
Pub Date : 2025-01-01Epub Date: 2024-05-16DOI: 10.1002/cm.21876
Izra Abbaali, Danny Truong, Dawn M Wetzel, Naomi S Morrissette
Protozoan parasites cause life-threatening infections in both humans and animals, including agriculturally significant livestock. Available treatments are typically narrow spectrum and are complicated by drug toxicity and the development of resistant parasites. Protozoan tubulin is an attractive target for the development of broad-spectrum antimitotic agents. The Medicines for Malaria Pathogen Box compound MMV676477 was previously shown to inhibit replication of kinetoplastid parasites, such as Leishmania amazonensis and Trypanosoma brucei, and the apicomplexan parasite Plasmodium falciparum by selectively stabilizing protozoan microtubules. In this report, we show that MMV676477 inhibits intracellular growth of the human apicomplexan pathogen Toxoplasma gondii with an EC50 value of ~50 nM. MMV676477 does not stabilize vertebrate microtubules or cause other toxic effects in human fibroblasts. The availability of tools for genetic studies makes Toxoplasma a useful model for studies of the cytoskeleton. We conducted a forward genetics screen for MMV676477 resistance, anticipating that missense mutations would delineate the binding site on protozoan tubulin. Unfortunately, we were unable to use genetics to dissect target interactions because no resistant parasites emerged. This outcome suggests that future drugs based on the MMV676477 scaffold would be less likely to be undermined by the emergence of drug resistance.
{"title":"Toxoplasma replication is inhibited by MMV676477 without development of resistance.","authors":"Izra Abbaali, Danny Truong, Dawn M Wetzel, Naomi S Morrissette","doi":"10.1002/cm.21876","DOIUrl":"10.1002/cm.21876","url":null,"abstract":"<p><p>Protozoan parasites cause life-threatening infections in both humans and animals, including agriculturally significant livestock. Available treatments are typically narrow spectrum and are complicated by drug toxicity and the development of resistant parasites. Protozoan tubulin is an attractive target for the development of broad-spectrum antimitotic agents. The Medicines for Malaria Pathogen Box compound MMV676477 was previously shown to inhibit replication of kinetoplastid parasites, such as Leishmania amazonensis and Trypanosoma brucei, and the apicomplexan parasite Plasmodium falciparum by selectively stabilizing protozoan microtubules. In this report, we show that MMV676477 inhibits intracellular growth of the human apicomplexan pathogen Toxoplasma gondii with an EC<sub>50</sub> value of ~50 nM. MMV676477 does not stabilize vertebrate microtubules or cause other toxic effects in human fibroblasts. The availability of tools for genetic studies makes Toxoplasma a useful model for studies of the cytoskeleton. We conducted a forward genetics screen for MMV676477 resistance, anticipating that missense mutations would delineate the binding site on protozoan tubulin. Unfortunately, we were unable to use genetics to dissect target interactions because no resistant parasites emerged. This outcome suggests that future drugs based on the MMV676477 scaffold would be less likely to be undermined by the emergence of drug resistance.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":"5-11"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11568068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140960164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lateral root (LR) organogenesis is regulated by cellular flux of auxin within pericycle cells, which depends on the membrane distribution and polar localization of auxin carrier proteins. The correct distribution of auxin carrier proteins relies on the intracellular trafficking of these proteins aided by filamentous actin as a track. However, the precise role of actin in lateral root development is still elusive. Here, using vegetative class actin isovariant mutants, we revealed that loss of actin isovariant ACT8 led to increased lateral root formation. The distribution of auxin within pericycle cells was altered in act8 mutant, primarily due to the altered distribution of AUX1 and PIN7. Interestingly, incorporation of act2 mutant in act8 background (act2act8) effectively nullified the LR phenotype observed in act8 mutant, indicating that ACT2 plays an important role in LR development. To explore further, we investigated the possibility that the act8 mutant's LR phenotype and cellular auxin distribution resulted from ACT2 overexpression. Consistent with the idea, enhanced lateral root formation, altered AUX1, PIN7 expression, and auxin distribution in pericycle cells were observed in ACT2 overexpression lines. Collectively, these results suggest that actin isovariant ACT2 but not ACT8 plays a pivotal role in regulating source-to-sink auxin distribution during lateral root organogenesis.
{"title":"Actin Isovariant ACT2-Mediated Cellular Auxin Homeostasis Regulates Lateral Root Organogenesis in Arabidopsis thaliana.","authors":"Aya Hanzawa, Arifa Ahamed Rahman, Abidur Rahman","doi":"10.1002/cm.21956","DOIUrl":"https://doi.org/10.1002/cm.21956","url":null,"abstract":"<p><p>Lateral root (LR) organogenesis is regulated by cellular flux of auxin within pericycle cells, which depends on the membrane distribution and polar localization of auxin carrier proteins. The correct distribution of auxin carrier proteins relies on the intracellular trafficking of these proteins aided by filamentous actin as a track. However, the precise role of actin in lateral root development is still elusive. Here, using vegetative class actin isovariant mutants, we revealed that loss of actin isovariant ACT8 led to increased lateral root formation. The distribution of auxin within pericycle cells was altered in act8 mutant, primarily due to the altered distribution of AUX1 and PIN7. Interestingly, incorporation of act2 mutant in act8 background (act2act8) effectively nullified the LR phenotype observed in act8 mutant, indicating that ACT2 plays an important role in LR development. To explore further, we investigated the possibility that the act8 mutant's LR phenotype and cellular auxin distribution resulted from ACT2 overexpression. Consistent with the idea, enhanced lateral root formation, altered AUX1, PIN7 expression, and auxin distribution in pericycle cells were observed in ACT2 overexpression lines. Collectively, these results suggest that actin isovariant ACT2 but not ACT8 plays a pivotal role in regulating source-to-sink auxin distribution during lateral root organogenesis.</p>","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645259","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}
Pub Date : 2022-04-01Epub Date: 2022-07-22DOI: 10.1002/cm.21715
Paul Trevorrow, Peter Gunning
{"title":"An interview with Peter Gunning - School of Medical Sciences, UNSW Sydney, Australia.","authors":"Paul Trevorrow, Peter Gunning","doi":"10.1002/cm.21715","DOIUrl":"https://doi.org/10.1002/cm.21715","url":null,"abstract":"","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":"79 4-5","pages":"24-25"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40488764","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}
Pub Date : 2022-04-01Epub Date: 2022-07-22DOI: 10.1002/cm.21717
John B Linehan, Jose Lucas Zepeda, Taylor A Mitchell, Elizabeth E LeClair
Actin assemblies are important in motile cells such as leukocytes which form dynamic plasma membrane extensions or podia. L-plastin (LCP1) is a leukocyte-specific calcium-dependent actin-bundling protein that, in mammals, is known to affect immune cell migration. Previously, we generated CRISPR/Cas9 engineered zebrafish lacking L-plastin (lcp1-/-) and reported that they had reduced survival to adulthood, suggesting that lack of L-plastin might negatively affect the immune system. To test this hypothesis, we examined the distribution and migration of neutrophils and macrophages in the transparent tail of early zebrafish larvae using cell-specific markers and an established wound-migration assay. Knockout larvae were similar to their heterozygous siblings in having equal body sizes and comparable numbers of neutrophils in caudal hematopoietic tissue at two days post-fertilization, indicating no gross defect in neutrophil production or developmental migration. When stimulated by a tail wound, all genotypes of neutrophils were equally migratory in a two-hour window. However for macrophages we observed both migration defects and morphological differences. L-plastin knockout macrophages still homed to wounds but were slower, less directional and had a star-like morphology with many leading and trailing projections. In contrast, wild type macrophages were faster, more directional, and had a more streamlined, slug-like morphology. Overall, these findings show that in larval zebrafish L-plastin knockout primarily affects the macrophage response with possible consequences for organismal immunity. Consistent with our observations, we propose a model in which cytoplasmic L-plastin negatively regulates macrophage integrin adhesion by holding these transmembrane heterodimers in a ‘clasped’, inactive form and is a necessary part of establishing macrophage polarity during chemokine-induced motility.
{"title":"Follow that cell: Leukocyte migration in L-plastin mutant zebrafish.","authors":"John B Linehan, Jose Lucas Zepeda, Taylor A Mitchell, Elizabeth E LeClair","doi":"10.1002/cm.21717","DOIUrl":"https://doi.org/10.1002/cm.21717","url":null,"abstract":"Actin assemblies are important in motile cells such as leukocytes which form dynamic plasma membrane extensions or podia. L-plastin (LCP1) is a leukocyte-specific calcium-dependent actin-bundling protein that, in mammals, is known to affect immune cell migration. Previously, we generated CRISPR/Cas9 engineered zebrafish lacking L-plastin (lcp1-/-) and reported that they had reduced survival to adulthood, suggesting that lack of L-plastin might negatively affect the immune system. To test this hypothesis, we examined the distribution and migration of neutrophils and macrophages in the transparent tail of early zebrafish larvae using cell-specific markers and an established wound-migration assay. Knockout larvae were similar to their heterozygous siblings in having equal body sizes and comparable numbers of neutrophils in caudal hematopoietic tissue at two days post-fertilization, indicating no gross defect in neutrophil production or developmental migration. When stimulated by a tail wound, all genotypes of neutrophils were equally migratory in a two-hour window. However for macrophages we observed both migration defects and morphological differences. L-plastin knockout macrophages still homed to wounds but were slower, less directional and had a star-like morphology with many leading and trailing projections. In contrast, wild type macrophages were faster, more directional, and had a more streamlined, slug-like morphology. Overall, these findings show that in larval zebrafish L-plastin knockout primarily affects the macrophage response with possible consequences for organismal immunity. Consistent with our observations, we propose a model in which cytoplasmic L-plastin negatively regulates macrophage integrin adhesion by holding these transmembrane heterodimers in a ‘clasped’, inactive form and is a necessary part of establishing macrophage polarity during chemokine-induced motility.","PeriodicalId":72766,"journal":{"name":"Cytoskeleton (Hoboken, N.J.)","volume":"79 4-5","pages":"26-37"},"PeriodicalIF":0.0,"publicationDate":"2022-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40488845","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}