Septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules

Nakos, Konstantinos; Alam, Md Noor A.; Radler, Megan R.; Kesisova, Ilona A.; Yang, Chao; Okletey, Joshua; Tomasso, Meagan R.; Padrick, Shae B.; Svitkina, Tatyana; Spiliotis, Elias T.

doi:10.1073/pnas.2202803119

Cited by 14 publications

(8 citation statements)

References 40 publications

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“…7 ). Our data provide a starting point to expand further investigations with a particular focus on actin–microtubule intersections ( Nakos et al, 2022 ).…”

Section: Discussionmentioning

confidence: 79%

Functional Inhibition of Katanin Affects Synaptic Plasticity

Lombino,

Schwarz,

Pechmann

et al. 2023

J. Neurosci.

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Dynamic microtubules critically regulate synaptic functions, but the role of microtubule severing in these processes is barely understood. Katanin is a neuronally expressed microtubule-severing complex regulating microtubule number and length in cell division or neurogenesis, however its potential role in synaptic functions has remained unknown. Studying mice from both sexes, we found that katanin is abundant in neuronal dendrites and can be detected at individual excitatory spine synapses. Overexpression of a dominant-negative ATPase-deficient katanin subunit to functionally inhibit severing, alters the growth of microtubules in dendrites, specifically at premature but not mature neuronal stages without affecting spine density. Notably, interference with katanin function prevented structural spine remodeling following single synapse glutamate uncaging and significantly affected the potentiation of AMPA-receptor-mediated excitatory currents after chemical induction of long-term potentiation. Furthermore, katanin inhibition reduced the invasion of microtubules into fully developed spines. Our data demonstrate that katanin-mediated microtubule-severing regulates structural and functional plasticity at synaptic sites.Significance StatementExcitatory spine synapses are rich in actin filaments that critically regulate structural and functional synaptic plasticity.In contrast, microtubules just transiently polymerize into dendritic spines. A synaptic role of dynamic microtubules is incompletely understood and the mechanisms that regulate microtubule rearrangement at synaptic sites have remained largely unknown. Here, we show that the microtubule severing enzyme katanin, known to keep microtubules in a dynamic state, is a component of synapses mediating functional and structural roles. Our data highlight an unnoted player of synapse function and connect microtubule severing with synaptic plasticity.

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“…7 ). Our data provide a starting point to expand further investigations with a particular focus on actin–microtubule intersections ( Nakos et al, 2022 ).…”

Section: Discussionmentioning

confidence: 79%

Functional Inhibition of Katanin Affects Synaptic Plasticity

Lombino,

Schwarz,

Pechmann

et al. 2023

J. Neurosci.

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“…Septins are well-equipped to mediate cytoskeletal crosstalk since they can bind to the cell membrane, actin and microtubules. 262 Recent research demonstrated roles of septins in mesenchymal and amoeboid single-cell migration 263,264 and in the regulation of endothelial and epithelial cell–cell adhesion. 265,266 Elucidating the biophysical mechanisms by which cytoskeletal crosstalk regulates cell migration is challenging due to the enormous molecular complexity of the cell and feedback between mechanical forces and biochemical signaling.…”

Section: The Road Aheadmentioning

confidence: 99%

How cytoskeletal crosstalk makes cells move: Bridging cell-free and cell studies

Conboy,

Istúriz Petitjean,

van der Net

et al. 2024

Biophysics Reviews

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Cell migration is a fundamental process for life and is highly dependent on the dynamical and mechanical properties of the cytoskeleton. Intensive physical and biochemical crosstalk among actin, microtubules, and intermediate filaments ensures their coordination to facilitate and enable migration. In this review, we discuss the different mechanical aspects that govern cell migration and provide, for each mechanical aspect, a novel perspective by juxtaposing two complementary approaches to the biophysical study of cytoskeletal crosstalk: live-cell studies (often referred to as top-down studies) and cell-free studies (often referred to as bottom-up studies). We summarize the main findings from both experimental approaches, and we provide our perspective on bridging the two perspectives to address the open questions of how cytoskeletal crosstalk governs cell migration and makes cells move.

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“…Septins are GTP-binding proteins which form hetero-hexa- or hetero-octamers that can assemble into filaments; they have diverse functions including membrane curvature sensing, or the regulation of actin and MT dynamics; in axons, they were demonstrated to regulate cargo transport, growth, branching and calcium homeostasis ( Hu et al, 2012 ; Ageta-Ishihara et al, 2013 ; Spiliotis, 2018 ; Katz et al, 2019 ; Deb et al, 2020 ; Woods and Gladfelter, 2021 ; Nakos et al, 2022 ).…”

Section: Roles and Regulations Of The Cytoskeleton In Axonsmentioning

confidence: 99%

How neurons maintain their axons long-term: an integrated view of axon biology and pathology

et al. 2023

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Axons are processes of neurons, up to a metre long, that form the essential biological cables wiring nervous systems. They must survive, often far away from their cell bodies and up to a century in humans. This requires self-sufficient cell biology including structural proteins, organelles, and membrane trafficking, metabolic, signalling, translational, chaperone, and degradation machinery—all maintaining the homeostasis of energy, lipids, proteins, and signalling networks including reactive oxygen species and calcium. Axon maintenance also involves specialised cytoskeleton including the cortical actin-spectrin corset, and bundles of microtubules that provide the highways for motor-driven transport of components and organelles for virtually all the above-mentioned processes. Here, we aim to provide a conceptual overview of key aspects of axon biology and physiology, and the homeostatic networks they form. This homeostasis can be derailed, causing axonopathies through processes of ageing, trauma, poisoning, inflammation or genetic mutations. To illustrate which malfunctions of organelles or cell biological processes can lead to axonopathies, we focus on axonopathy-linked subcellular defects caused by genetic mutations. Based on these descriptions and backed up by our comprehensive data mining of genes linked to neural disorders, we describe the ‘dependency cycle of local axon homeostasis’ as an integrative model to explain why very different causes can trigger very similar axonopathies, providing new ideas that can drive the quest for strategies able to battle these devastating diseases.

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Septins mediate a microtubule–actin crosstalk that enables actin growth on microtubules

Cited by 14 publications

References 40 publications

Functional Inhibition of Katanin Affects Synaptic Plasticity

Functional Inhibition of Katanin Affects Synaptic Plasticity

How cytoskeletal crosstalk makes cells move: Bridging cell-free and cell studies

How neurons maintain their axons long-term: an integrated view of axon biology and pathology

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