KIF1C, an RNA transporting kinesin-3, undergoes liquid-liquid phase separation through its C-terminal disordered domain DOI Creative Commons
Qi Geng, Jakia Jannat Keya, Takashi Hotta

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 23, 2023

Abstract The spatial distribution of mRNA is critical for local control protein production. Recent studies have identified the kinesin-3 family member KIF1C as an RNA transporter. However, it not clear how interacts with molecules. Here, we show that KIF1C’s C-terminal tail domain intrinsically disordered region (IDR) containing a prion-like (PLD) unique compared to tails other kinesin members. In cells, constructs undergo reversible formation dynamic puncta display physical properties liquid condensates and incorporate molecules in sequence-selective manner. IDR necessary sufficient driving liquid-liquid phase separation (LLPS) but condensate can be modulated by adjacent coiled-coil segments. purified undergoes LLPS vitro at near-endogenous nM concentrations salt-dependent Deletion abolished ability disrupted cargoes cell periphery. Our work thus uncovers intrinsic correlation between activity its role addition, first motor reported LLPS, our reveals previously uncharacterized mode motor-cargo interaction extends understanding behavior cytoskeletal proteins.

Language: Английский

Cortical wiring by synapse type–specific control of local protein synthesis DOI
C. Bernard, David Exposito-Alonso, Martijn Selten

et al.

Science, Journal Year: 2022, Volume and Issue: 378(6622)

Published: Nov. 24, 2022

Neurons use local protein synthesis to support their morphological complexity, which requires independent control across multiple subcellular compartments up the level of individual synapses. We identify a signaling pathway that regulates proteins required form excitatory synapses on parvalbumin-expressing (PV

Language: Английский

Citations

48

mRNA transport, translation, and decay in adult mammalian central nervous system axons DOI Creative Commons

Jane Jung,

Jiyeon Ohk,

Hye Young Kim

et al.

Neuron, Journal Year: 2022, Volume and Issue: 111(5), P. 650 - 668.e4

Published: Dec. 29, 2022

Language: Английский

Citations

39

Mapping of multiple neurotransmitter receptor subtypes and distinct protein complexes to the connectome DOI Creative Commons
Piero Sanfilippo, Alexander Kim, Anuradha Bhukel

et al.

Neuron, Journal Year: 2024, Volume and Issue: 112(6), P. 942 - 958.e13

Published: Jan. 22, 2024

Neurons express various combinations of neurotransmitter receptor (NR) subunits and receive inputs from multiple neuron types expressing different neurotransmitters. Localizing NR to specific synaptic has been challenging. Here, we use epitope-tagged endogenous subunits, expansion light-sheet microscopy, electron microscopy (EM) connectomics molecularly characterize synapses in Drosophila. We show that directionally selective motion-sensitive neurons, NRs elaborated a highly stereotyped molecular topography with localized domains receiving cell-type-specific inputs. Developmental studies suggested or complexes them other membrane proteins determine patterns In support this model, identify transmembrane protein selectively associated subset spatially restricted demonstrate its requirement for synapse formation through genetic analysis. propose mechanisms regulate the precise spatial distribution provide cartography specifying connections onto dendrites.

Language: Английский

Citations

15

Regulation and outcomes of localized RNA translation DOI Creative Commons
Alexander N. Gasparski, Devon E. Mason, Konstadinos Moissoglu

et al.

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2022, Volume and Issue: 13(6)

Published: Feb. 14, 2022

Spatial segregation of mRNAs in the cytoplasm cells is a well-known biological phenomenon that widely observed diverse species spanning different kingdoms life. In mammalian cells, localization has been documented and studied quite extensively highly polarized most notably neurons, where localized function to direct protein production at sites are distant from soma. Recent studies have strikingly revealed large proportion cellular transcriptome exhibits distributions even lack an obvious need for long-range transport, such as fibroblasts or epithelial cells. This review focuses on emerging concepts regarding functional outcomes mRNA targeting We also discuss regulatory mechanisms controlling these events, with emphasis role cell mechanics organization cytoskeleton. article categorized under: Translation > Regulation RNA Export Localization Localization.

Language: Английский

Citations

31

Specialized Ribosomes in Health and Disease DOI Open Access
Sarah Miller, Clinton C. MacDonald, Morgana K. Kellogg

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(7), P. 6334 - 6334

Published: March 28, 2023

Ribosomal heterogeneity exists within cells and between different cell types, at specific developmental stages, occurs in response to environmental stimuli. Mounting evidence supports the existence of specialized ribosomes, or changes ribosome that regulate translation a group transcripts. These alterations have been shown affect affinity ribosomes for certain mRNAs change cotranslational folding nascent polypeptides exit tunnel. The identification requires incorporation ribosomal proteins modifications rRNA and/or protein lead(s) physiologically relevant translation. In this review, we summarize specialization mammals discuss their relevance several human diseases.

Language: Английский

Citations

22

The kinesin-3 KIF1C undergoes liquid-liquid phase separation for accumulation of specific transcripts at the cell periphery DOI Creative Commons
Qi Geng, Jakia Jannat Keya, Takashi Hotta

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(15), P. 3192 - 3213

Published: June 19, 2024

Language: Английский

Citations

7

The use of electrical stimulation to enhance recovery following peripheral nerve injury DOI Creative Commons

Paige B. Hardy,

Bonnie Y. Wang,

K. Ming Chan

et al.

Muscle & Nerve, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 30, 2024

Abstract Peripheral nerve injury is common and can have devastating consequences. In severe cases, functional recovery often poor despite surgery. This primarily due to the exceedingly slow rate of regeneration at only 1–3 mm/day. The local environment in distal stump supportive regrowth deteriorates over time target end organs become atrophic. To overcome these challenges, investigations into treatments capable accelerating are great clinical relevance an active area research. One intervention that has shown promise perioperative electrical stimulation. Postoperative stimulation helps expedite Wallerian degeneration process reduces delays caused by staggered site injury. By contrast, preoperative “conditioning” increases along trunk. Over past two decades, a rich body literature emerged provides molecular insights mechanism which impacts regeneration. result upregulation regeneration‐associated genes neuronal accelerated transport axon front for regrowth. efficacy brief on patients with peripheral injuries was demonstrated number randomized controlled trials compressive, transection traction injuries. As approved equipment deliver this treatment becoming available, it may be feasible deploy novel wide range settings.

Language: Английский

Citations

5

A multi-omics view of neuronal subcellular protein synthesis DOI
Chao Sun, Erin M. Schuman

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 80, P. 102705 - 102705

Published: March 11, 2023

Language: Английский

Citations

11

The brain's dark transcriptome: Sequencing RNA in distal compartments of neurons and glia DOI Creative Commons
Seth A. Ament, Alexandros Poulopoulos

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 81, P. 102725 - 102725

Published: May 15, 2023

Transcriptomic approaches are powerful strategies to map the molecular diversity of cells in brain. Single-cell genomic atlases have now been compiled for entire mammalian brains. However, complementary techniques only just beginning subcellular transcriptomes from distal cellular compartments. We review single-cell datasets alongside subtranscriptome data brain explore development and diversity. discuss how RNA-seq misses transcripts localized away cell bodies, which form 'dark transcriptome' brain: a collection subtranscriptomes dendrites, axons, growth cones, synapses, endfeet with important roles function. Recent advances transcriptome sequencing reveal these elusive pools RNA. outline success stories date uncovering constituent neurons glia, as well present emerging toolkit that is accelerating pace discovery.

Language: Английский

Citations

10

mRNA trafficking to synapses and memory formation DOI
Oswald Steward, Shannon Farris

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0