Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
The COPII cargo adapter SEC24C is essential for neuronal homeostasis
Bo Wang, … , David Ginsburg, Mondira Kundu
Bo Wang, … , David Ginsburg, Mondira Kundu
Published June 25, 2018
Citation Information: J Clin Invest. 2018;128(8):3319-3332. https://doi.org/10.1172/JCI98194.
View: Text | PDF
Research Article Development Neuroscience

The COPII cargo adapter SEC24C is essential for neuronal homeostasis

  • Text
  • PDF
Abstract

SEC24 family members are components of the coat protein complex II (COPII) machinery that interact directly with cargo or with other adapters to ensure proper sorting of secretory cargo into COPII vesicles. SEC24C is 1 of 4 mammalian SEC24 paralogs (SEC24A–D), which segregate into 2 subfamilies on the basis of sequence homology (SEC24A/SEC24B and SEC24C/SEC24D). Here, we demonstrate that postmitotic neurons, unlike professional secretory cells in other tissues, are exquisitely sensitive to loss of SEC24C. Conditional KO of Sec24c in neural progenitors during embryogenesis caused perinatal mortality and microcephaly, with activation of the unfolded protein response and apoptotic cell death of postmitotic neurons in the murine cerebral cortex. The cell-autonomous function of SEC24C in postmitotic neurons was further highlighted by the loss of cell viability caused by disrupting Sec24c expression in forebrain neurons of mice postnatally and in differentiated neurons derived from human induced pluripotent stem cells. The neuronal cell death associated with Sec24c deficiency was rescued in knockin mice expressing Sec24d in place of Sec24c. These data suggest that SEC24C is a major cargo adapter for COPII-dependent transport in postmitotic neurons in developing and adult brains and that its functions overlap at least partially with those of SEC24D in mammals.

Authors

Bo Wang, Joung Hyuck Joo, Rebecca Mount, Brett J. W. Teubner, Alison Krenzer, Amber L. Ward, Viraj P. Ichhaporia, Elizabeth J. Adams, Rami Khoriaty, Samuel T. Peters, Shondra M. Pruett-Miller, Stanislav S. Zakharenko, David Ginsburg, Mondira Kundu

×

Figure 2

The brains of Sec24c-deficient mice contain fewer neurons than brains of control mice.

Options: View larger image (or click on image) Download as PowerPoint
The brains of Sec24c-deficient mice contain fewer neurons than brains of...
(A) Representative images of layers II–VI in control (n = 3) and Sec24cNes-cKO (n = 3) mice at P0, as delineated by expression of the callosal neuron marker SATB2, the layer V marker CTIP2, and the layer VI marker TBR1. Scale bar: 100 μm. (B) Thickness of designated cortical layers (mean ± SEM) and numbers of neurons within those layers (mean ± SEM) from Sec24cNes-cKO (n = 3) and control (n = 3) mice. (C) Representative images of immunostained brain sections showing ISLET1/2+ neurons in the striatum and NKX2.1+ neurons in the globus pallidus of control (n = 3) and Sec24cNes-cKO (n = 3) mice at P0. Scale bar: 500 μm. (D) Mean area (± SEM) covered by and mean number (± SEM) of ISLET1/2+ and NKX2.1+ cells in the striatum and globus pallidus of Sec24cNes-cKO (n = 3) and control (n = 3) mice. GP, globus pallidus. *P < 0.05 and **P < 0.01, by Student’s t test.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts