Kinesin family member 2A gates nociception.

Animals Mice Kinesins / genetics Neurons / physiology Nociception Pain Repressor Proteins / genetics
CP: Neuroscience Kif2a axonal degeneration microtubules nociception

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
31 10 2023
Historique:
received: 23 03 2023
revised: 23 08 2023
accepted: 27 09 2023
medline: 6 11 2023
pubmed: 18 10 2023
entrez: 18 10 2023
Statut: ppublish

Résumé

Nociceptive axons undergo remodeling as they innervate their targets during development and in response to environmental insults and pathological conditions. How is nociceptive morphogenesis regulated? Here, we show that the microtubule destabilizer kinesin family member 2A (Kif2a) is a key regulator of nociceptive terminal structures and pain sensitivity. Ablation of Kif2a in sensory neurons causes hyperinnervation and hypersensitivity to noxious stimuli in young adult mice, whereas touch sensitivity and proprioception remain unaffected. Computational modeling predicts that structural remodeling is sufficient to explain the phenotypes. Furthermore, Kif2a deficiency triggers a transcriptional response comprising sustained upregulation of injury-related genes and homeostatic downregulation of highly specific channels and receptors at the late stage. The latter effect can be predicted to relieve the hyperexcitability of nociceptive neurons, despite persisting morphological aberrations, and indeed correlates with the resolution of pain hypersensitivity. Overall, we reveal a critical control node defining nociceptive terminal structure, which is regulating nociception.

Identifiants

DOI: 10.1016/j.celrep.2023.113257 PMID: 37851573
pubmed: 37851573
pii: S2211-1247(23)01269-X
doi: 10.1016/j.celrep.2023.113257
pii:
doi:

Substances chimiques

Kinesins EC 3.6.4.4
Repressor Proteins 0
KIF2A protein, mouse EC 3.6.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

113257

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Swagata Dey (S)

Department of Biomolecular Sciences and Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel.

Omer Barkai (O)

Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel; F.M. Kirby Neurobiology Center, Boston Children's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Irena Gokhman (I)

Department of Biomolecular Sciences and Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel.

Sapir Suissa (S)

Department of Biomolecular Sciences and Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel.

Rebecca Haffner-Krausz (R)

Department of Veterinary Resources, Weizmann Institute of Science, Rehovot 76100, Israel.

Noa Wigoda (N)

Bioinformatics Unit, Life Science Core Facilities, Weizmann Institute of Science, Rehovot 76100, Israel.

Ester Feldmesser (E)

Bioinformatics Unit, Life Science Core Facilities, Weizmann Institute of Science, Rehovot 76100, Israel.

Shifra Ben-Dor (S)

Bioinformatics Unit, Life Science Core Facilities, Weizmann Institute of Science, Rehovot 76100, Israel.

Andrew Kovalenko (A)

Department of Biomolecular Sciences and Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel.

Alexander Binshtok (A)

Department of Medical Neurobiology, Institute for Medical Research Israel-Canada, The Hebrew University-Hadassah School of Medicine, Jerusalem 91120, Israel; The Edmond and Lily Safra Center for Brain Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.

Avraham Yaron (A)

Department of Biomolecular Sciences and Department of Molecular Neuroscience, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: avraham.yaron@weizmann.ac.il.

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Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Kinesin family member 2A gates nociception.
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Kinesin family member 2A gates nociception.
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines de tissu nerveux › Protéines associées aux microtubules › Kinésine › Kinesin family member 2A gates nociception.
Recherchemedicale.com › Cellules › Neurones › Kinesin family member 2A gates nociception.
Recherchemedicale.com › Phénomènes psychologiques › Processus mentaux › Perception › Perception de la douleur › Nociception › Kinesin family member 2A gates nociception.
Recherchemedicale.com › Phénomènes physiologiques de l'appareil locomoteur et du système nerveux › Phénomènes physiologiques du système nerveux › Sensation › Douleur › Kinesin family member 2A gates nociception.
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Kinesin family member 2A gates nociception.