The Dynamic Interplay Between ATP/ADP Levels and Autophagy Sustain Neuronal Migration in Vivo

Overview

Journal Elife

Specialty Biology

Date 2020 Sep 28

PMID 32985978

Citations 18

Authors

Cedric Bressan

Alessandra Pecora

Dave Gagnon

Marina Snapyan

Simon Labrecque

Paul De Koninck

Martin Parent

Armen Saghatelyan

Affiliations

Soon will be listed here.

Abstract

Cell migration is a dynamic process that entails extensive protein synthesis and recycling, structural remodeling, and considerable bioenergetic demand. Autophagy is one of the pathways that maintain cellular homeostasis. Time-lapse imaging of autophagosomes and ATP/ADP levels in migrating cells in the rostral migratory stream of mouse revealed that decreases in ATP levels force cells into the stationary phase and induce autophagy. Pharmacological or genetic impairments of autophagy in neuroblasts using either bafilomycin, inducible conditional mice, or CRISPR/Cas9 gene editing decreased cell migration due to the longer duration of the stationary phase. Autophagy is modulated in response to migration-promoting and inhibiting molecular cues and is required for the recycling of focal adhesions. Our results show that autophagy and energy consumption act in concert in migrating cells to dynamically regulate the pace and periodicity of the migratory and stationary phases to sustain neuronal migration.

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References

Zhou T, Zhang B, Wei P, Du Y, Zhou H, Yu M . Energy metabolism analysis reveals the mechanism of inhibition of breast cancer cell metastasis by PEG-modified graphene oxide nanosheets. Biomaterials. 2014; 35(37):9833-9843. DOI: 10.1016/j.biomaterials.2014.08.033. View

Kroemer G, Marino G, Levine B . Autophagy and the integrated stress response. Mol Cell. 2010; 40(2):280-93. PMC: 3127250. DOI: 10.1016/j.molcel.2010.09.023. View

Sharifi M, Mowers E, Drake L, Collier C, Chen H, Zamora M . Autophagy Promotes Focal Adhesion Disassembly and Cell Motility of Metastatic Tumor Cells through the Direct Interaction of Paxillin with LC3. Cell Rep. 2016; 15(8):1660-72. PMC: 4880529. DOI: 10.1016/j.celrep.2016.04.065. View

Eskelinen E . To be or not to be? Examples of incorrect identification of autophagic compartments in conventional transmission electron microscopy of mammalian cells. Autophagy. 2007; 4(2):257-60. DOI: 10.4161/auto.5179. View

Bakhshetyan K, Saghatelyan A . Tracking neuronal migration in adult brain slices. Curr Protoc Neurosci. 2015; 71:3.28.1-3.28.13. DOI: 10.1002/0471142301.ns0328s71. View

Ayala R, Shu T, Tsai L . Trekking across the brain: the journey of neuronal migration. Cell. 2007; 128(1):29-43. DOI: 10.1016/j.cell.2006.12.021. View

Kenific C, Stehbens S, Goldsmith J, Leidal A, Faure N, Ye J . NBR1 enables autophagy-dependent focal adhesion turnover. J Cell Biol. 2016; 212(5):577-90. PMC: 4772495. DOI: 10.1083/jcb.201503075. View

Petherick K, Conway O, Mpamhanga C, Osborne S, Kamal A, Saxty B . Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy. J Biol Chem. 2015; 290(18):11376-83. PMC: 4416842. DOI: 10.1074/jbc.C114.627778. View

Cosker K, Segal R . Neuronal signaling through endocytosis. Cold Spring Harb Perspect Biol. 2014; 6(2). PMC: 3941234. DOI: 10.1101/cshperspect.a020669. View

10.

Hill S, Colon-Ramos D . The Journey of the Synaptic Autophagosome: A Cell Biological Perspective. Neuron. 2020; 105(6):961-973. DOI: 10.1016/j.neuron.2020.01.018. View

11.

Gstrein T, Edwards A, Pristoupilova A, Leca I, Breuss M, Pilat-Carotta S . Mutations in Vps15 perturb neuronal migration in mice and are associated with neurodevelopmental disease in humans. Nat Neurosci. 2018; 21(2):207-217. PMC: 5897053. DOI: 10.1038/s41593-017-0053-5. View

12.

Jung C, Jun C, Ro S, Kim Y, Otto N, Cao J . ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009; 20(7):1992-2003. PMC: 2663920. DOI: 10.1091/mbc.e08-12-1249. View

13.

Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T . LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci. 2004; 117(Pt 13):2805-12. DOI: 10.1242/jcs.01131. View

14.

Waclaw R, Ehrman L, Pierani A, Campbell K . Developmental origin of the neuronal subtypes that comprise the amygdalar fear circuit in the mouse. J Neurosci. 2010; 30(20):6944-53. PMC: 2882074. DOI: 10.1523/JNEUROSCI.5772-09.2010. View

15.

Webb D, Parsons J, Horwitz A . Adhesion assembly, disassembly and turnover in migrating cells -- over and over and over again. Nat Cell Biol. 2002; 4(4):E97-100. DOI: 10.1038/ncb0402-e97. View

16.

Yang Z, Klionsky D . Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2009; 22(2):124-31. PMC: 2854249. DOI: 10.1016/j.ceb.2009.11.014. View

17.

Hyder F, Rothman D, Bennett M . Cortical energy demands of signaling and nonsignaling components in brain are conserved across mammalian species and activity levels. Proc Natl Acad Sci U S A. 2013; 110(9):3549-54. PMC: 3587194. DOI: 10.1073/pnas.1214912110. View

18.

Tantama M, Martinez-Francois J, Mongeon R, Yellen G . Imaging energy status in live cells with a fluorescent biosensor of the intracellular ATP-to-ADP ratio. Nat Commun. 2013; 4:2550. PMC: 3852917. DOI: 10.1038/ncomms3550. View

19.

Li W, Hu N, Lei F, Wei S, Rong J, Zhuang H . Autophagy inhibits endothelial progenitor cells migration via the regulation of MMP2, MMP9 and uPA under normoxia condition. Biochem Biophys Res Commun. 2015; 466(3):376-80. DOI: 10.1016/j.bbrc.2015.09.031. View

20.

Kim J, Kundu M, Viollet B, Guan K . AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol. 2011; 13(2):132-41. PMC: 3987946. DOI: 10.1038/ncb2152. View