The Wnt/Ca 2+ pathway is involved in interneuronal communication mediated by tunneling nanotubes

Autor: Gonzalo Córdova, Jessica Y Vargas, Frida Loria, Chiara Zurzolo, Masato Hasegawa, Geeske M. van Woerden, Yuan-Ju Wu, Sebastien Bellow, Takashi Nonaka, Capucine Trollet, Sylvie Syan
Přispěvatelé: Trafic membranaire et Pathogénèse, Institut Pasteur [Paris], Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Tokyo Metropolitan University [Tokyo] (TMU), Bioaxial, Department of Neuroscience [Rotterdam, the Netherlands], Erasmus University Medical Center [Rotterdam] (Erasmus MC), Expertise Center for Neurodevelopmental Disorders [Rotterdam, the Netherlands] (ENCORE), This work was supported by the Agence Nationale de la Recherche [ANR‐16‐CE16‐0019‐01], Fondation pour la Recherche Médicale [FRM‐2016‐DEQ20160334896] and grants from LECMA‐Vaincre Alzheimer and France Alzheimer foundations to CZ. Funding from E‐Rare/ERANET (project SIRD) to CT. Grant‐in‐Aid for Scientific Research on Innovative Areas (Brain Protein Aging and Dementia Control) (JP26117005) from MEXT and Grant‐in‐Aid for Scientific Research on Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) (JP14533254) from AMED and JST CREST (JP18071300) to MH. Grant from Brain Science Foundation to TN. FL was recipient of Marie Skłodowska‐Curie individual fellowships and is funded through the Marie Skłodowska‐Curie Action COFUND 2015 (EU project 713366 – InterTalentum). Y‐JW was recipient of Pasteur‐Roux‐Cantarini fellowships., The authors are thankful to Dr. Seng Zhu and Shaarvari Bhat for their help in the acquisition of live imaging experiments., Institut Pasteur [Paris] (IP), ANR-16-CE16-0019,Neurotunn,Role des nanotubes membranaires dans la propagation d'agrégats protéiques impliqués dans les maladie neurodégénératives(2016), Department of Neuropathology and Cell Biology, Tokyo Metropolitan Institute of Medical Science, Biologie Cellulaire du Parasitisme, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Pharmacologie Chimique et Génétique (UPCG - UMR_S 640/UMR 8151), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Biologia e Patologia Cellulare e Moleculare, Università degli studi di Napoli Federico II, Neurosciences, Centre de Recherche en Myologie, Vargas, J. Y., Loria, F., Wu, Y. -J., Cordova, G., Nonaka, T., Bellow, S., Syan, S., Hasegawa, M., van Woerden, G. M., Trollet, C., Zurzolo, C.
Rok vydání: 2019
Předmět:
MESH: Signal Transduction
Wnt Protein
[SDV]Life Sciences [q-bio]
MESH: Mice
Knockout

tunneling nanotubes
MESH: Nanotubes/chemistry
Mice
Cell Communication
MESH: Cell Communication
0302 clinical medicine
MESH: Animals
MESH: Wnt Proteins/metabolism
Cells
Cultured

ComputingMilieux_MISCELLANEOUS
MESH: Neurons/cytology
Mice
Knockout

0303 health sciences
CaMKII
General Neuroscience
Vesicle
Neurodegeneration
Wnt signaling pathway
musculoskeletal system
3. Good health
Cell biology
intercellular communication
MESH: Calcium/metabolism
Intracellular
Signal Transduction
MESH: Cells
Cultured

Gene isoform
Wnt pathway
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
MESH: Cell Membrane/metabolism
Biology
MESH: Calcium Signaling
MESH: Calcium-Calmodulin-Dependent Protein Kinase Type 2/physiology
General Biochemistry
Genetics and Molecular Biology

MESH: Neurons/physiology
03 medical and health sciences
tunneling nanotube
α-synuclein
MESH: Mice
Inbred C57BL

Ca2+/calmodulin-dependent protein kinase
medicine
Calcium Signaling
MESH: Mice
Molecular Biology
Actin
030304 developmental biology
General Immunology and Microbiology
Animal
Cell Membrane
MESH: Actins/metabolism
Neuron
medicine.disease
Mice
Inbred C57BL

Nanotube
Cell culture
Calcium
Calcium-Calmodulin-Dependent Protein Kinase Type 2
030217 neurology & neurosurgery
Zdroj: EMBO Journal
EMBO Journal, EMBO Press, 2019, 38 (23), ⟨10.15252/embj.2018101230⟩
The EMBO Journal
EMBO Journal, 2019, 38 (23), ⟨10.15252/embj.2018101230⟩
EMBO Journal, 38(23):e101230. Wiley-Blackwell
ISSN: 1460-2075
0261-4189
DOI: 10.15252/embj.2018101230
Popis: International audience; Tunneling nanotubes (TNTs) are actin-based transient tubular connections that allow direct communication between distant cells. TNTs play an important role in several physiological (development, immunity, and tissue regeneration) and pathological (cancer, neurodegeneration, and pathogens transmission) processes. Here, we report that the Wnt/Ca2+ pathway, an intracellular cascade that is involved in actin cytoskeleton remodeling, has a role in TNT formation and TNT-mediated transfer of cargoes. Specifically, we found that Ca2+ /calmodulin-dependent protein kinase II (CaMKII), a transducer of the Wnt/Ca2+ pathway, regulates TNTs in a neuronal cell line and in primary neurons. We identified the β isoform of CaMKII as a key molecule in modulating TNT formation and transfer, showing that this depends on the actin-binding activity of the protein. Finally, we found that the transfer of vesicles and aggregated α-synuclein between primary neurons can be regulated by the activation of the Wnt/Ca2+ pathway. Our findings suggest that Wnt/Ca2+ pathway could be a novel promising target for therapies designed to impair TNT-mediated propagation of pathogens.
Databáze: OpenAIRE