Pyramidal neuron morphogenesis requires a septin network that stabilizes filopodia and suppresses lamellipodia during neurite initiation DOI Open Access
Megan R. Radler, Xiaonan Liu,

Megan Peng

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: June 19, 2022

Summary Pyramidal neurons are the major cell type of forebrain, consisting a pyramidally shaped soma with axonal and apicobasal dendritic processes. It is poorly understood how neuronal morphs from sphere to pyramid, while generating neurites proper shape orientation. Here, we discovered that spherical somata immature neurite-less possess circumferential wreath-like network septin filaments, which promotes myosin II localization suppresses Arp2/3 activity at base filopodial actin bundles. The facilitates neurite formation by stabilizing nascent filopodia, mature neurites, concomitantly maintains consolidated suppressing extension lamellipodia. We show this function critical for morphogenesis spatial orientation pyramidal their in vitro vivo. Therefore, somatic cytoskeleton provides key morphogenetic mechanism neuritogenesis development neurons. Highlights - A controls Septins promote suppress lamellipodial protrusions, respectively scaffold exclude Development requires septins vivo eTOC Radler et al report new neurons, mediated stabilizes filopodia lamellipodia differentially controlling Arp2/3.

Language: Английский

Septins as membrane influencers: direct play or in association with other cytoskeleton partners DOI Creative Commons
Béatrice Benoit, Christian Poüs,

Anita Baillet

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Feb. 17, 2023

The cytoskeleton comprises three polymerizing structures that have been studied for a long time, actin microfilaments, microtubules and intermediate filaments, plus more recently investigated dynamic assemblies like septins or the endocytic-sorting complex required transport (ESCRT) complex. These filament-forming proteins control several cell functions through crosstalks with each other membranes. In this review, we report recent works address how bind to membranes, influence their shaping, organization, properties functions, either by binding them directly indirectly elements.

Language: Английский

Citations

24

Identification of ceRNA network to explain the mechanism of cognitive dysfunctions induced by PS NPs in mice DOI Creative Commons
Chu Chen,

Yaling Zhang,

Qingping Liu

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2022, Volume and Issue: 241, P. 113785 - 113785

Published: June 24, 2022

Plastics breaking down of larger plastics into smaller ones (microplastics and nanoplastic) as potential threats to the ecosystem. Previous studies demonstrate that central nervous system (CNS) is a vulnerable target nanoplastics. However, potentially epigenetic biomarkers nanoplastic neurotoxicity in rodent models are still unknown. The present research aimed determine role competing endogenous RNA (ceRNA) process polystyrene nanoplastics (PS NPs) exposure-induced nerve injury. study was designed investigate whether 25 nm PS NPs could cause learning dysfunction elucidate underlying mechanisms mice. A total 40 mice were divided 4 groups exposed (0, 10, 25, 50 mg/kg). Chronic toxicity introduced by administration oral gavage for 6 months. evaluation included assessment their behavior, pathological investigation determination levels reactive oxygen species (ROS) DNA damage. RNA-Seq performed detect expression circRNAs, miRNAs mRNAs PFC samples treated with 0 mg/kg NPs. results indicated exposure caused dose-dependent cognitive decline. ROS damage increased following 987 mRNAs, 29 67 circRNAs demonstrated significant differences between groups. Functional enrichment analyses may induce major injury synaptic function. 96 which associated identified. network containing 27 19 35 dysfunction-related constructed. provided insight molecular events induction dysfunction.

Language: Английский

Citations

26

Lipid packing and local geometry influence septin curvature sensing DOI Creative Commons
Brandy N. Curtis, Ellysa J. D. Vogt, C. J. Edelmaier

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 16, 2025

Septins assemble into scaffolds that direct cell growth and morphology are often localized to the plasma membrane. While septins preferentially bind convex membranes via amphipathic helices, their assembly on varied geometries in cells suggests additional localization cues. We tested hypothesis lipid composition directs septin through packing properties. Lipid mixtures varying were designed by molecular dynamics simulations incorporated onto supported bilayers measure adsorption vitro. strongly favor loosely-packed, disordered but geometry cues act conjunction with this membrane property. Introducing tighter disrupted structures a curvature dependent manner, specifically limiting retention along flat regions of This work demonstrates defects jointly regulate highlights how multiple properties integrated control organization cytoskeleton. Localization cytoskeleton is controlled regulatory factors, curvature, charge. In study, changes modulate found impact assemblies vitro cells.

Language: Английский

Citations

0

Phosphoregulation of the septin cytoskeleton in neuronal development and disease DOI

Bailey Werner,

Smita Yadav

Cytoskeleton, Journal Year: 2022, Volume and Issue: 80(7-8), P. 275 - 289

Published: Sept. 21, 2022

Abstract Septins are highly conserved GTP‐binding proteins that oligomerize and form higher order structures. The septin cytoskeleton plays an important role in cellular organization, intracellular transport, cytokinesis. Kinase‐mediated phosphorylation of septins regulates various aspects their function, localization, dynamics. enriched the mammalian nervous system where they contribute to neurodevelopment neuronal function. Emerging research has implicated aberrant changes several human diseases. mechanisms through which by kinases contributes dysfunction neurological disorders poorly understood represent question for future with therapeutic implications. This review summarizes current state knowledge diversity interact phosphorylate septins, delineates how phosphoregulation impacts dynamics, describes disorders.

Language: Английский

Citations

15

The Axonal Actin Filament Cytoskeleton: Structure, Function, and Relevance to Injury and Degeneration DOI
Gianluca Gallo

Molecular Neurobiology, Journal Year: 2024, Volume and Issue: 61(8), P. 5646 - 5664

Published: Jan. 13, 2024

Language: Английский

Citations

3

Septin and actin contributions to endothelial cell–cell junctions and monolayer integrity DOI Open Access
Kyung Soon Kim, Olivia L. Mooren, Michael D. Onken

et al.

Cytoskeleton, Journal Year: 2022, Volume and Issue: 80(7-8), P. 228 - 241

Published: Oct. 7, 2022

Septins in endothelial cells (ECs) have important roles supporting the integrity of monolayer. Cell-cell junctions EC monolayers are highly dynamic, with continuous retractions and protrusions. Depletion septins ECs leads to disruption cell-cell junctions, which composed VE-cadherin other junctional proteins. In monolayers, concentrated at plasma membrane sites contact, curved- scallop-shaped patterns. These membrane-associated septin accumulations located regions positive curvature, those often associated immediately adjacent actin-rich protrusions negative curvature. associate directly lipids, based on findings site-specific mutations ECs, is consistent biochemical cell biological studies systems. Loss monolayer, gaps form between cells. The number breadth contacts decreases, frequency retractions, ruffles, edges also decreases. addition, loss decreased amounts F-actin cortical membrane, along increased stress fibers cytoplasm. Endothelial monolayer from transendothelial electric resistance (TEER) levels migration (TEM) by immune cancer cells, owing A current working model that assembly filaments curvature contributes a mechanical footing or base for actin-based protrusive forces generated adjoining membrane. Specific molecular interactions actin components cytoskeleton may be contributors. Regulators promote support as part feedback loop filaments.

Language: Английский

Citations

10

Sculpting the dendritic landscape: Actin, microtubules, and the art of arborization DOI Creative Commons

Vasileios R. Ouzounidis,

Bram Prevo, Dhanya K. Cheerambathur

et al.

Current Opinion in Cell Biology, Journal Year: 2023, Volume and Issue: 84, P. 102214 - 102214

Published: Aug. 4, 2023

Dendrites are intricately designed neuronal compartments that play a vital role in the gathering and processing of sensory or synaptic inputs. Their diverse elaborate structures distinct features organization function. Central to generation these dendritic arbors is cytoskeleton. In this review, we delve into current progress toward our understanding how dendrite generated maintained, focusing on actin microtubule

Language: Английский

Citations

5

Pyramidal neuron morphogenesis requires a septin network that stabilizes filopodia and suppresses lamellipodia during neurite initiation DOI Creative Commons
Megan R. Radler, Xiaonan Liu,

Megan Peng

et al.

Current Biology, Journal Year: 2022, Volume and Issue: 33(3), P. 434 - 448.e8

Published: Dec. 19, 2022

Language: Английский

Citations

9

Microtubule-associated septin complexes modulate kinesin and dynein motility with differential specificities DOI Creative Commons
Ayana Suber, Md Noor A. Alam,

Κωνσταντίνος Νάκος

et al.

Journal of Biological Chemistry, Journal Year: 2023, Volume and Issue: 299(9), P. 105084 - 105084

Published: July 24, 2023

Long-range membrane traffic is guided by microtubule-associated proteins and posttranslational modifications, which collectively comprise a code. The regulatory principles of this code how it orchestrates the motility kinesin dynein motors are largely unknown. Septins large family GTP-binding proteins, assemble into complexes that associate with microtubules. Using single-molecule in vitro assays, we tested SEPT2/6/7, SEPT2/6/7/9, SEPT5/7/11 affect motilities constitutively active kinesins KIF5C KIF1A dynein-dynactin-bicaudal D (DDB) motor complex. We found SEPT2/6/7 potent inhibitor DDB KIF5C, preventing mainly their association also inhibits obstructing stepping along On SEPT2/6/7/9-coated microtubules, inhibition dampened SEPT9, alone enhances KIF1A, showing individual septin subunits determine properties complexes. Strikingly, differs from permitting immobilizing to microtubule lattice. In hippocampal neurons, filamentous SEPT5 colocalizes somatodendritic microtubules underlie Golgi membranes lack SEPT6. Depletion disrupts morphology polarization ribbons shaft somato-proximal dendrites, consistent tethering SEPT5/7/11. Collectively, these results suggest have differential specificities regulation positioning motors. posit septins an integral part microtubule-based spatially controls traffic.

Language: Английский

Citations

5

BORG family proteins in physiology and human disease DOI Open Access

Meagan R. Tomasso,

Shae B. Padrick

Cytoskeleton, Journal Year: 2023, Volume and Issue: 80(7-8), P. 182 - 198

Published: July 1, 2023

The binder of rho GTPases (BORG)/Cdc42 effector proteins (Cdc42EP) family is composed five Rho GTPase binding whose functions and mechanism actions are emerging interest. Here, we review recent findings pertaining to the as a whole consider how these change our understanding cellular organization. Recent studies have implicated BORGs in both fundamental physiology human diseases, mainly cancers. An pattern suggests that BORG members cancer-promoting properties related their ability regulate cytoskeleton, with many impacting organization acto-myosin stress fibers. This consistent broader literature indicating regulators septin actin cytoskeleton networks. exact through which modify not clear, but here few data-supported speculative possibilities. Finally, delve into Cdc42 modifies function cells. remains open-ended Cdc42's effects on appear cell type- state-dependent. Collectively, data point importance suggest themes regulation.

Language: Английский

Citations

3