Hitchhiking Across Kingdoms: Cotransport of Cargos in Fungal, Animal, and Plant Cells

Annual Review of Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 38(1), P. 155 - 178

Published: July 29, 2022

Eukaryotic cells across the tree of life organize their subcellular components via intracellular transport mechanisms. In canonical transport, myosin, kinesin, and dynein motor proteins interact with cargos adaptor move along filamentous actin or microtubule tracks. contrast to this mode, hitchhiking is a newly discovered mode in which cargo attaches itself an already-motile rather than directly associating protein itself. Many including messenger RNAs, complexes, organelles hitchhike on membrane-bound cargos. Hitchhiking-like behaviors have been shown impact cellular processes local translation, long-distance signaling, organelle network reorganization. Here, we review instances fungal, animal, plant discuss potential evolutionary importance these different contexts.

Language: Английский

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Polarity-dependent expression and localization of secretory glucoamylase mRNA in filamentous fungal cells

Microbiological Research, Journal Year: 2024, Volume and Issue: 282, P. 127653 - 127653

Published: Feb. 23, 2024

In multinuclear and multicellular filamentous fungi little is known about how mRNAs encoding secreted enzymes are transcribed localized spatiotemporally. To better understand this process we analyzed mRNA GlaA, a glucoamylase in large amounts by the industrial fungus Aspergillus oryzae, MS2 system, which can be visualized living cells. We found that glaA was significantly near hyphal tip septum, sites of protein secretion, polarity-dependent expression localization manners. also revealed exhibits long-range dynamics vicinity endoplasmic reticulum (ER) manner dependent on microtubule motor proteins kinesin-1 kinesin-3, but independent early endosomes. Moreover, elucidated although to stress granules (SGs) processing bodies (PBs) under high temperature, not seen ER stress, suggesting there different regulatory mechanisms SG PB temperature stress. Collectively, study uncovers dynamic mechanism secretory enzyme fungi.

Language: Английский

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Cardiac Involvement and TBCK‐Related Neurodevelopmental Disorder: Is It a New Feature of This Condition?

American Journal of Medical Genetics Part A, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

ABSTRACT TBCK (TBC1 Domain‐Containing Kinase) encodes a protein playing role in actin organization and cell growth/proliferation via the mTOR signaling pathway. Deleterious biallelic variants cause Hypotonia, infantile, with psychomotor retardation characteristic facies 3. We report on three affected sibs, also displaying cardiac malformations. The parents, consanguineous couple of first cousins, were referred to schedule invasive diagnosis for their sixth pregnancy. They known carry pathogenic c.1532G>A variant. variant was originally identified homozygosity second children couple, both affected. One presented right‐sided aortic arch. other had Tetralogy Fallot. Present pregnancy ultrasound revealed cystic hygroma hypoplastic nasal bone, not previously reported this condition. Chromosomal microarray analysis found no imbalance 8.6% runs homozygosity. Whole exome sequencing confirmed without additional or candidate variants. Fetal echocardiography left ventricle arch hypoplasia. opted termination. Fetopsy sonographic findings aorta arising from right corpus callosum agenesis. Interestingly, phenotype segregates involvement might be considered new feature causing

Language: Английский

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A novel, rapidly progressive ataxia due to a spontaneous Myo5a mutation in mice impairs transport proteins and alters mitochondria

The FASEB Journal, Journal Year: 2025, Volume and Issue: 39(5)

Published: March 1, 2025

Abstract Spontaneous mouse mutants have helped define genetic contributions to many phenotypes. Here we report a spontaneous Novel Ataxic Phenotype in mice. Ataxia findings were evident at post‐natal day 11 NAP mice and rapidly worsened, resulting preweaning lethality. Using genome sequencing genome‐wide mapping, identified 3′ donor splice variant exon 14 of Myo5a , encoding an actin‐based motor protein. The (c.1752g>a) excises ablates MYO5A protein expression, which is implicated intracellular transport Griscelli syndrome type I humans. displayed expansion PAX6‐positive cells the external granule layer cerebellum, mass spectrometry analysis cerebellar extracts uncovered differentially abundant proteins involved short‐range organelle transport, specifically with early endosomes. lysates primary neurons, provide evidence for interaction between ANKFY1, known effector endosomal protein, RAB5A. We also found neurons from had elongated mitochondria, linking mitochondrial homeostasis. This allele provides new insight into function developmental neuropathology.

Language: Английский

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Multi-organelle-mediated mRNA localization in neurons and links to disease

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102332 - 102332

Published: March 7, 2025

Brain function requires precise spatiotemporal regulation of the neuronal proteome. To allow adaptation proteome in distal outposts neurons, mRNAs are transported into neurites for localized translation. This mRNA localization and local translation is crucial neuron maintenance, dysregulation these processes can contribute to neurological disease. Recently, organelles have emerged as key players regulating dendrites axons. In this review, we discuss current evidence open questions organelle-mediated localization. We highlight an emerging model which multiple create orchestrate a subcellular microenvironment that support selective seems essential maintaining organellar health, mutations many involved proteins lead various disorders.

Language: Английский

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TBCK-deficiency leads to compartment-specific mRNA and lysosomal trafficking defects in patient-derived neurons

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

Published: March 7, 2025

ABSTRACT Monogenic pediatric neurodegenerative disorders can reveal fundamental cellular mechanisms that underlie selective neuronal vulnerability. TBCK-Encephaloneuronopathy (TBCKE) is a rare autosomal recessive disorder caused by stop-gain variants in the TBCK gene. Clinically, patients show evidence of profound neurodevelopmental delays, but also symptoms progressive encephalopathy and motor neuron disease. Yet, physiological role protein remains unclear. We report human TBCKE model, derived from iPSCs homozygous for Boricua variant (p.R126X). Using unbiased proteomic analyses neurons, we find interacts with PPP1R21, C12orf4, Cryzl1, consistent being part FERRY mRNA transport complex. Loss leads to depletion C12ORF4 levels across multiple cell types, suggesting may play regulating at least some members preferentially, not exclusively, localizes surface endolysosomal vesicles colocalize lysosomes. Furthermore, TBCK-deficient neurons have reduced content axonal compartment relative soma. lysosomal dynein/dynactin adapter JIP4, which functionally exhibiting striking retrograde trafficking defects. Hence, our work reveals mediate mRNA, particularly along lysosomes compartments. TBCK-deficiency compartment-specific defects likely contribute preferential susceptibility neurodegeneration.

Language: Английский

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Neurogenetic disorders associated with mutations in the FERRY complex: a novel disease class?

Biology Open, Journal Year: 2025, Volume and Issue: 14(3)

Published: March 10, 2025

The five-subunit endosomal Rab5 and RNA/ribose intermediary (FERRY) complex is a newly described protein consisting of TBCK, PPP1R21, FERRY3 (previously C12orf4), CRYZL1, GATD1. FERRY proposed to function as effector shuttle mRNA the cell periphery for local translation, process especially important in cells with far reaching processes. Interestingly, three members are associated ultra-rare neurogenetic disorders. Mutation TBCK causes syndrome, mutation PPP1R21 PPP1R21-related intellectual disability, results an autosomal recessive disability. Neurologic disorders have yet be GATD1 or CRYZL1. Here, we provide review each complex-related neurologic disorder draw clinical comparisons between disease states. We also discuss data from current cellular animal models available study these disorders, which notably disparate scattered across different types systems. Taken together, explore possibility that diseases may represent one shared class, could further understood by combining comparing known information about individual disease. If true, this substantial implications on our understanding role treatment strategies affected individuals, allowing researchers, clinicians, patient organizations maximize utility research efforts resources support patients

Language: Английский

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Decoding TBCK: from bioinformatic insights of domain architecture to disease implications

Frontiers in Biophysics, Journal Year: 2025, Volume and Issue: 3

Published: April 4, 2025

TBCK is an essential protein in neurodevelopment. Mutations the gene are associated with Syndrome, a genetic neurological disorder characterized by global developmental delay. enigmatic multidomain that contains pseudokinase domain, TBC (Tre2-Bub2-Cdc16) and rhodanese-like domain. Emerging evidence increasingly links to multiple cellular processes, including mTOR signaling, autophagy, lysosomal function, mitochondrial maintenance. This review consolidates recent advances our understanding of TBCK, emphasizing comparative sequence analysis, structural modeling, its functions. Our analysis shows both kinase domain likely lack catalytic activity instead primarily function as scaffolds or regulatory domains. The all conserved residues, suggesting it may act GTPase-activating (GAP). These functional hypotheses provide foundation for further investigations into TBCK’s physiological pathological roles.

Language: Английский

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The role of mitochondrial mRNA translation in cellular communication

Journal of Cell Science, Journal Year: 2025, Volume and Issue: 138(9)

Published: May 1, 2025

ABSTRACT Mitochondria are dynamic and heterogeneous organelles that rewire their network metabolic functions in response to changing cellular needs. To this end, mitochondria integrate a plethora of incoming signals influence cell fate survival. A crucial highly regulated node cell–mitochondria communication is the translation nuclear-encoded mitochondrial mRNAs. By controlling monitoring spatio-temporal these mRNAs, cells can rapidly adjust function meet demands, optimise ATP production regulate organelle biogenesis turnover. In Review, we focus on how RNA-binding proteins recognise mRNAs acutely modulate rate nutrient availability. We further discuss relevance localised for subsets polarised cells. Finally, highlight quality control mechanisms monitor process at surface connections mitophagy stress responses. propose processes collectively contribute specialisation signalling function.

Language: Английский

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The role of mitochondrial RNA association for mitochondrial homeostasis in neurons

Biochemical Journal, Journal Year: 2024, Volume and Issue: 481(3), P. 119 - 139

Published: Jan. 29, 2024

The sub-compartmentalization of cellular processes is especially important in highly polarized cells such as neurons, their function rely on complex morphology. association RNAs to the mitochondrial surface a conserved feature from yeast humans and it regulates several aspects physiology and, hence, functions. In mitochondria are emerging platforms for RNA transport local protein translation. this review, we discuss how localization helps sustain function, can support homeostasis, distal parts neuron, neuronal activity.

Language: Английский

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