Restoration of striatal neuroprotective pathways by kinase inhibitor treatment of Parkinsons linked-LRRK2 mutant mice DOI Creative Commons
Ebsy Jaimon, Yu‐En Lin, Francesca Tonelli

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 3, 2024

Parkinsons disease-associated, activating mutations in Leucine Rich Repeat Kinase 2 (LRRK2) block primary cilia formation cholinergic and parvalbumin interneurons astrocytes the striatum, decreasing production of GDNF NRTN neuroprotective factors that normally support dopaminergic neuron viability. We show here 3 month-dietary administration MLi-2 LRRK2 kinase inhibitor restores Hedgehog-responsive by these neurons; are also restored on neurons pedunculopontine nucleus. Importantly, we detect recovery striatal processes decreased stress-triggered Hedgehog signaling nigral neurons. Thus, pathogenic LRRK2-driven loss is reversible post-mitotic astrocytes, which suggests early specific inhibitors may have significant therapeutic benefit for patients future.

Language: Английский

The neuronal cilium – a highly diverse and dynamic organelle involved in sensory detection and neuromodulation DOI Creative Commons
Nathalie Jurisch‐Yaksi, Dagmar Wachten, Jay Gopalakrishnan

et al.

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: 47(5), P. 383 - 394

Published: April 4, 2024

Cilia are fascinating organelles that act as cellular antennae, sensing the environment. gained significant attention in late 1990s after their dysfunction was linked to genetic diseases known ciliopathies. Since then, several breakthrough discoveries have uncovered mechanisms underlying cilia biogenesis and function. Like most cells animal kingdom, neurons also harbor cilia, which enriched neuromodulatory receptors. Yet, how neuronal modulate physiology behavior remains poorly understood. By comparing ciliary biology between sensory central nervous systems (CNS), we provide new perspectives on functions of brain physiology.

Language: Английский

Citations

10
Cilia directionality reveals a slow reverse movement of principal neurons for positioning and lamina refinement in the cerebral cortex DOI Creative Commons
Juan Yang,

Soheila Mirhosseiniardakani,

Liyan Qiu

et al.

Development, Journal Year: 2025, Volume and Issue: 152(5)

Published: March 1, 2025

Currently, not much is known about neuronal positioning and the roles of primary cilia in postnatal neurodevelopment. We show that principal neurons undergo marked changes orientation, concurrent with neuron mouse cerebral cortex. Primary early- late-born compact layers display opposite orientations, while loose laminae are predominantly oriented toward pia. In contrast, astrocytes interneurons, nucleated brain regions do specific directionality. further discovered cell bodies inside-out laminated spanning from hippocampal CA1 region to neocortex a slow 'reverse movement' for lamina refinement. Furthermore, selective disruption function forebrain leads altered lamination gyrification retrosplenial cortex formed by reverse movement. Collectively, this study identifies movement as fundamental process refines casts light on evolutionary transition three-layered allocortices six-layered neocortices.

Language: Английский

Citations

1
GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade DOI Creative Commons
Madison F. Walker, Jingyi Zhang,

William Steiner

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(8), P. e3002685 - e3002685

Published: Aug. 13, 2024

During Hedgehog (Hh) signal transduction in development and disease, the atypical G protein-coupled receptor (GPCR) SMOOTHENED (SMO) communicates with GLI transcription factors by binding protein kinase A catalytic subunit (PKA-C) physically blocking its enzymatic activity. Here, we show that GPCR 2 (GRK2) orchestrates this process during endogenous mouse zebrafish Hh pathway activation primary cilium. Upon SMO activation, GRK2 rapidly relocalizes from ciliary base to shaft, triggering phosphorylation PKA-C interaction. Reconstitution studies reveal enables active bind directly. Lastly, SMO-GRK2-PKA underlies a range of cellular vivo models. Thus, ensuing inactivation are critical initiating events for intracellular steps signaling. More broadly, our study suggests an expanded role GRKs enabling direct interactions diverse effectors.

Language: Английский

Citations

5
Mechanism and regulation of kinesin motors DOI
Ahmet Yıldız

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 11, 2024

Language: Английский

Citations

5
Sonic Hedgehog activates prostaglandin signaling to stabilize primary cilium length DOI Creative Commons
Shariq S. Ansari, Miriam E. Dillard, Yan Zhang

et al.

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(9)

Published: June 10, 2024

Sonic Hedgehog (SHH) is a driver of embryonic patterning that, when corrupted, triggers developmental disorders and cancers. SHH effector responses are organized through primary cilia (PC) that grow retract with the cell cycle in response to extracellular cues. Disruption PC homeostasis corrupts regulation, placing significant pressure on pathway maintain ciliary fitness. Mechanisms by which robustness ensured SHH-stimulated cells not yet known. Herein, we reveal crosstalk circuit induced activation Phospholipase A2α drives E-type prostanoid receptor 4 (EP4) signaling ensure function stabilize length. We demonstrate blockade SHH-EP4 destabilizes cyclic AMP (cAMP) equilibrium, slows transport, reduces length, attenuates induction. Accordingly, Ep4-/- mice display shortened neuroepithelial altered SHH-dependent neuronal fate specification. Thus, initiates coordination between distinct receptors length for robust downstream signaling.

Language: Английский

Citations

4
The intraflagellar transport cycle DOI
Samuel E. Lacey, Gaia Pigino

Nature Reviews Molecular Cell Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 13, 2024

Language: Английский

Citations

4
Molecular Mechanisms of Cold Stress Response in Cotton: Transcriptional Reprogramming and Genetic Strategies for Tolerance DOI
Washu Dev, Fahmida Sultana, Hongge Li

et al.

Plant Science, Journal Year: 2025, Volume and Issue: unknown, P. 112390 - 112390

Published: Jan. 1, 2025

Language: Английский

Citations

0
Prominosomes - a particular class of extracellular vesicles containing prominin-1/CD133? DOI Creative Commons
Jana Karbanová,

Kristina Thamm,

Christine A. Fargeas

et al.

Journal of Nanobiotechnology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 29, 2025

Extracellular membrane vesicles (EVs) offer promising values in various medical fields, e.g., as biomarkers liquid biopsies or native (or bioengineered) biological nanocarriers tissue engineering, regenerative medicine and cancer therapy. Based on their cellular origin EVs can vary considerably composition diameter. Cell studies mammalian prominin-1, a cholesterol-binding glycoprotein, have helped to reveal new donor membranes sources of EVs. For instance, small originate from microvilli primary cilia, while large might be produced by transient structures such retracting extremities cells during the mitotic rounding process, midbody at end cytokinesis. Here, we will highlight subcellular origins prominin-1+ EVs, also called prominosomes, potential mechanism(s) regulating formation. We further discuss molecular characteristics notably those that direct effect release process directly implicated cell reprogramming stem cells. Prominin-1+ mediate intercellular communication embryonic development adult homeostasis healthy individuals, disseminating information diseases.

Language: Английский

Citations

0
Muscarinic acetylcholine receptor 3 localized to primary endothelial cilia regulates blood pressure and cognition DOI Creative Commons

Hannah C. Saternos,

Kathleen Forero,

Mahmood A. Meqdad

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Jan. 30, 2025

Language: Английский

Citations

0
Axonemal microtubule dynamics in the assembly and disassembly of cilia DOI Creative Commons
Yi Zhang, Mu He, Junmin Pan

et al.

Biochemical Society Transactions, Journal Year: 2025, Volume and Issue: 53(1)

Published: Jan. 31, 2025

Cilia and eukaryotic flagella (exchangeable terms) function in cell motility signaling, which are pivotal for development physiology. dysfunction can lead to ciliopathies. usually assembled quiescent and/or differentiated cells undergo disassembly when enter cycle or response environmental stresses. contain a microtubule-based structure termed axoneme that comprises nine outer doublet microtubules with without pair of central microtubules, is ensheathed by the ciliary membrane. Regulation axonemal microtubule dynamics tightly associated assembly disassembly. In this short review, we discuss recent findings on regulation microtubule-binding proteins modulating kinesins during

Language: Английский

Citations

0