The Spectrin-Actin-Based Periodic Cytoskeleton as a Conserved Nanoscale Scaffold and Ruler of the Neural Stem Cell Lineage

Meghan Hauser; Rui Yan; Wan Li; Nicole A Repina; David V Schaffer; Ke Xu

doi:10.1016/j.celrep.2018.07.005

The Spectrin-Actin-Based Periodic Cytoskeleton as a Conserved Nanoscale Scaffold and Ruler of the Neural Stem Cell Lineage

Cell Rep. 2018 Aug 7;24(6):1512-1522. doi: 10.1016/j.celrep.2018.07.005.

Authors

Meghan Hauser¹, Rui Yan¹, Wan Li¹, Nicole A Repina², David V Schaffer³, Ke Xu⁴

Affiliations

¹ Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.
² Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA.
³ Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
⁴ Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Division of Molecular Biophysics and Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA. Electronic address: xuk@berkeley.edu.

Abstract

Through three-dimensional STORM super-resolution microscopy, we resolve the spectrin-actin-based membrane cytoskeleton of neural stem cells (NSCs) and NSC-derived neurons, astrocytes, and oligodendrocytes. We show that undifferentiated NSCs are capable of forming patches of locally periodic, one-dimensional (1D) membrane cytoskeleton with ∼180 nm periodicity. Such periodic structures become increasingly ordered and long-ranging as the NSCs mature into terminally differentiated neuronal and glial cell types, and, during this process, distinct 1D periodic "strips" dominate the flat 2D membranes. Moreover, we report remarkable alignment of the periodic cytoskeletons between abutting cells at axon-axon and axon-oligodendrocyte contacts and identify two adhesion molecules, neurofascin and L1CAM, as candidates to drive this nanoscale alignment. We thus show that a conserved 1D periodic membrane cytoskeletal motif serves as a nanoscale scaffold and ruler to mediate the physical interactions between cell types of the NSC lineage.

Keywords: cell adhesion molecule; cell-cell interaction; membrane cytoskeleton; neural stem cell; periodic cytoskeleton; spectrin-actin cytoskeleton; super-resolution microscopy.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Actin Cytoskeleton / metabolism*
Cell Lineage
Humans
Neural Stem Cells / metabolism*
Spectrin / metabolism*

Substances

Spectrin

Grants and funding

R01 NS087253/NS/NINDS NIH HHS/United States