CaltechAUTHORS
  A Caltech Library Service

Temporal changes in plasma membrane lipid content induce endocytosis to regulate developmental epithelial-to-mesenchymal transition

Piacentino, Michael L. and Hutchins, Erica J. and Andrews, Cecelia J. and Bronner, Marianne E. (2020) Temporal changes in plasma membrane lipid content induce endocytosis to regulate developmental epithelial-to-mesenchymal transition. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20201021-071531181

[img] PDF - Submitted Version
Creative Commons Attribution Non-commercial No Derivatives.

7Mb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20201021-071531181

Abstract

Epithelial-to-mesenchymal transition (EMT) is a dramatic change in cellular physiology during development and metastasis which involves coordination between cell signaling, adhesion, and membrane protrusions. These processes all involve dynamic changes in the plasma membrane, yet how membrane lipid content regulates membrane function during developmental EMT remains incompletely understood. By screening for differential expression of lipid-modifying genes over the course of EMT in avian neural crest, we have identified the ceramide-producing enzyme neutral sphingomyelinase 2 (nSMase2) as a critical regulator of a developmental EMT. nSMase2 expression begins at the onset of EMT, and in vivo knockdown experiments demonstrate that nSMase2 is necessary for neural crest migration. Further, we find that nSMase2 promotes Wnt and BMP signaling, and is required to activate the mesenchymal gene expression program. Mechanistically, we show that nSMase2 is sufficient to induce endocytosis, and that inhibition of endocytosis mimics nSMase2 knockdown. Our results support a model in which nSMase2 is expressed at the onset of neural crest EMT to produce ceramide and induce membrane curvature, thus increasing endocytosis of Wnt and BMP signaling complexes and activating pro-migratory gene expression. These results highlight the critical role of plasma membrane lipid metabolism in regulating transcriptional changes during developmental EMT programs.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.10.18.344523DOIDiscussion Paper
ORCID:
AuthorORCID
Piacentino, Michael L.0000-0003-1773-031X
Hutchins, Erica J.0000-0002-4316-0333
Bronner, Marianne E.0000-0003-4274-1862
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. Posted October 19, 2020. We would like to thank Megan Martik, Erdinç Sezgin, Justin Bois, and Steven Wilbert for valuable discussion on experiment design and analysis, and Alexis Camacho-Avila and Gabriel da Silva Pescador for technical support. We thank Catherine Berlot, Anna-Katerina Hadjantonakis, Randall Moon, and Elisa Martí for sharing reagents. Confocal imaging was supported by the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation to the Biological Imaging Facility. Funding for this work comes from the National Institutes of Health grants K99DE029240 to M.L.P., K99DE028592 to E.J.H, R01DE027538 and R01DE027568 to M.E.B, and from the Caltech Summer Undergraduate Research Fellowship (SURF) to C.J.A. Author Contributions: Conceptualization: M.L.P. and M.E.B. Experiment design: M.L.P., E.J.H., and M.E.B. Experimentation: M.L.P., E.J.H., and C.J.A. Data analysis: M.L.P. and C.J.A. Data interpretation: M.L.P., E.J.H., and M.E.B. Manuscript preparation: M.L.P. and M.E.B. Manuscript editing: E.J.H. The authors declare no competing interests. Data Availability: All data that support the findings of this study are available from the corresponding author upon reasonable request. The Smpd3 mRNA sequence has been submitted to GenBank (Accession # Pending). Code Availability: All data analysis code used in this study are available from the corresponding author upon reasonable request.
Funders:
Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
NIHK99DE029240
NIHK99DE028592
NIHR01DE027538
NIHR01DE027568
Caltech Summer Undergraduate Research Fellowship (SURF)UNSPECIFIED
Record Number:CaltechAUTHORS:20201021-071531181
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201021-071531181
Official Citation:Temporal changes in plasma membrane lipid content induce endocytosis to regulate developmental epithelial-to-mesenchymal transition. Michael L Piacentino, Erica J Hutchins, Cecelia J Andrews, Marianne E. Bronner. bioRxiv 2020.10.18.344523; doi: https://doi.org/10.1101/2020.10.18.344523
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106175
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Oct 2020 16:58
Last Modified:21 Oct 2020 16:58

Repository Staff Only: item control page