Publications by authors named "Satish Bodakuntla"

Cryogenic electron microscopy (cryo-EM) and electron tomography (cryo-ET) have become a critical tool for studying viral particles. Cryo-EM has enhanced our understanding of viral assembly and replication processes at a molecular resolution. Meanwhile, cryo-ET has been used to investigate how viruses attach to and invade host cells.

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  • SARS-CoV-2, the virus causing COVID-19, affects the body by interacting with host-cell receptors via its spike protein (S protein).
  • The study reveals that the S protein triggers significant changes in platelets, which can lead to their permanent activation, a factor contributing to coagulopathies in COVID-19 patients.
  • Researchers found that the S protein binds to specific platelet integrins that induce filopodia formation, suggesting that these interactions play a role in the disease's severity and blood clotting complications.
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  • SARS-CoV-2, the virus causing COVID-19, interacts with host-cell receptors through its spike protein, which is crucial for its high pathogenicity.
  • The study reveals that the spike protein can cause platelets to deform and activate irreversibly, suggesting a direct link between the virus and coagulopathies in COVID-19 patients.
  • Researchers found that the spike protein binds to specific integrin receptors on platelets, indicating that this interaction may play a role in the severe coagulation issues associated with COVID-19.
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Mutations in the brain-specific β-tubulin 4A (TUBB4A) gene cause a broad spectrum of diseases, ranging from dystonia (DYT-TUBB4A) to hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC). Currently, the mechanisms of how variants lead to this pleiotropic manifestation remain elusive. Here, we investigated whether mutations causing either DYT-TUBB4A (p.

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  • * This study used advanced imaging techniques to observe how organelles and cytoskeletal structures change in real-time at axon branches in mouse neurons.
  • * Findings suggest that axon branches act as specialized areas for protein synthesis and organelle concentration, playing a crucial role in axon growth and the overall complexity of neural networks.
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The microtubule cytoskeleton forms complex macromolecular assemblies with a range of microtubule-associated proteins (MAPs) that have fundamental roles in cell architecture, division and motility. Determining how an individual MAP modulates microtubule behaviour is an important step in understanding the physiological roles of various microtubule assemblies. To characterize how MAPs control microtubule properties and functions, we developed an approach allowing for medium-throughput analyses of MAPs in cell-free conditions using lysates of mammalian cells.

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Background: In the panel of genes commonly associated with inherited macrothrombocytopenia, an important fraction encodes key cytoskeletal proteins such as tubulin isotypes, the building blocks of microtubules. Macrothrombocytopenia-causing mutations have been identified in the TUBB1 and TUBA4A genes, emphasizing their importance in the formation of platelets and their marginal band, a unique microtubule ring-like structure that supports the platelet typical disc-shaped morphology. This raised the hypothesis that other tubulin isotypes normally expressed in platelets could play a similar role in their formation.

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  • * Effective branching relies on coordinated cellular functions, including cytoskeletal dynamics, transport system, and energy production specifically tailored for forming branches.
  • * The review focuses on how the arrangement of cytoskeletal components, endoplasmic reticulum, and mitochondria at branching sites differ from the main axon shaft, highlighting the importance of membrane and cytoskeletal remodeling.
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Tubulin polyglutamylation is a post-translational modification of the microtubule cytoskeleton, which is generated by a variety of enzymes with different specificities. The "tubulin code" hypothesis predicts that modifications generated by specific enzymes selectively control microtubule functions. Our recent finding that excessive accumulation of polyglutamylation in neurons causes their degeneration and perturbs axonal transport provides an opportunity for testing this hypothesis.

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Neurodegenerative diseases lead to a progressive demise of neuronal functions that ultimately results in neuronal death. Besides a large variety of molecular pathways that have been linked to the degeneration of neurons, dysfunctions of the microtubule cytoskeleton are common features of many human neurodegenerative disorders. Yet, it is unclear whether microtubule dysfunctions are causative, or mere bystanders in the disease progression.

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One important aspect of studies of the microtubule cytoskeleton is the investigation of microtubule behavior in in vitro reconstitution experiments. They allow the analysis of the intrinsic properties of microtubules, such as dynamics, and their interactions with microtubule-associated proteins (MAPs). The "tubulin code" is an emerging concept that points to different tubulin isotypes and various posttranslational modifications (PTMs) as regulators of microtubule properties and functions.

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Microtubule cytoskeleton exists in various biochemical forms in different cells due to tubulin posttranslational modifications (PTMs). Tubulin PTMs are known to affect microtubule stability, dynamics, and interaction with MAPs and motors in a specific manner, widely known as tubulin code hypothesis. At present, there exists no tool that can specifically mark tubulin PTMs in living cells, thus severely limiting our understanding of their dynamics and cellular functions.

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Neurons are highly complex cells that heavily rely on intracellular transport to distribute a range of functionally essential cargoes within the cell. Post-translational modifications of tubulin are emerging as mechanisms for regulating microtubule functions, but their impact on neuronal transport is only marginally understood. Here, we have systematically studied the impact of post-translational polyglutamylation on axonal transport.

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Axonal transport is a process essential for neuronal function and survival that takes place on the cellular highways-the microtubules. It requires three major components: the microtubules that serve as tracks for the transport, the motor proteins that drive the movement, and the transported cargoes with their adaptor proteins. Axonal transport could be controlled by tubulin posttranslational modifications, which by decorating specific microtubule tracks could determine the specificity of cargo delivery inside neurons.

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Microtubules, as integral part of the eukaryotic cytoskeleton, exert numerous essential functions in cells. A mechanism to control these diverse functions are the posttranslational modifications of tubulin. Despite being known for decades, relatively little insight into the cellular functions of these modifications has been gained so far.

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Microtubule-associated proteins (MAPs) were initially discovered as proteins that bind to and stabilize microtubules. Today, an ever-growing number of MAPs reveals a more complex picture of these proteins as organizers of the microtubule cytoskeleton that have a large variety of functions. MAPs enable microtubules to participate in a plethora of cellular processes such as the assembly of mitotic and meiotic spindles, neuronal development, and the formation of the ciliary axoneme.

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  • In vitro studies on microtubules are revealing how different types of tubulin and their modifications impact microtubule dynamics and protein interactions.
  • A new purification protocol enables researchers to obtain tubulin with controlled post-translational modifications, which is crucial for studying the tubulin code.
  • This protocol, applicable to various cell types, enhances the functionality of purified tubulin and can be integrated with other experimental techniques, taking about 13 days for cell growth and 6-7 hours for purification.
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Sperm cells are highly specialized mammalian cells, and their biogenesis requires unique intracellular structures. Perturbation of spermatogenesis often leads to male infertility. Here, we assess the role of a post-translational modification of tubulin, glutamylation, in spermatogenesis.

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Posttranslational modifications of tubulin are emerging regulators of microtubule functions. We have shown earlier that upregulated polyglutamylation is linked to rapid degeneration of Purkinje cells in mice with a mutation in the deglutamylating enzyme CCP1. How polyglutamylation leads to degeneration, whether it affects multiple neuron types, or which physiological processes it regulates in healthy neurons has remained unknown.

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Microtubules are central elements of the eukaryotic cytoskeleton that often function as part of branched networks. Current models for branching include nucleation of new microtubules from severed microtubule seeds or from γ-tubulin recruited to the side of a pre-existing microtubule. Here, we found that microtubules can be directly remodelled into branched structures by the microtubule-remodelling factor SSNA1 (also known as NA14 or DIP13).

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DNA alkylating agents form the first line of cancer chemotherapy. They not only kill cells but also behave as potential carcinogens. MNU, a DNA methylating agent, is well known to induce mammary tumours in rodents.

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As essential components of the eukaryotic cytoskeleton, microtubules fulfill a variety of functions that can be temporally and spatially controlled by tubulin posttranslational modifications. Tubulin glycylation has so far been mostly found on motile cilia and flagella, where it is involved in the stabilization of the axoneme. In contrast, barely anything is known about the role of glycylation in primary cilia because of limitations in detecting this modification in these organelles.

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