Conserved role for Ataxin-2 in mediating endoplasmic reticulum dynamics

Urko del Castillo, Megan M. Gnazzo, Christopher G. Sorensen Turpin, Ken C.Q. Nguyen, Emily Semaya, Yuwan Lam, Matthew A. de Cruz, Joshua N. Bembenek, David H. Hall, Blake Riggs, Vladimir I. Gelfand, Ahna R. Skop

Research output: Contribution to journalArticle

Abstract

Ataxin-2, a conserved RNA-binding protein, is implicated in the late-onset neurodegenerative disease Spinocerebellar ataxia type-2 (SCA2). SCA2 is characterized by shrunken dendritic arbors and torpedo-like axons within the Purkinje neurons of the cerebellum. Torpedo-like axons have been described to contain displaced endoplasmic reticulum (ER) in the periphery of the cell; however, the role of Ataxin-2 in mediating ER function in SCA2 is unclear. We utilized the Caenorhabditis elegans and Drosophila homologs of Ataxin-2 (ATX-2 and DAtx2, respectively) to determine the role of Ataxin-2 in ER function and dynamics in embryos and neurons. Loss of ATX-2 and DAtx2 resulted in collapse of the ER in dividing embryonic cells and germline, and ultrastructure analysis revealed unique spherical stacks of ER in mature oocytes and fragmented and truncated ER tubules in the embryo. ATX-2 and DAtx2 reside in puncta adjacent to the ER in both C. elegans and Drosophila embryos. Lastly, depletion of DAtx2 in cultured Drosophila neurons recapitulated the shrunken dendritic arbor phenotype of SCA2. ER morphology and dynamics were severely disrupted in these neurons. Taken together, we provide evidence that Ataxin-2 plays an evolutionary conserved role in ER dynamics and morphology in C. elegans and Drosophila embryos during development and in fly neurons, suggesting a possible SCA2 disease mechanism.

Original languageEnglish (US)
JournalTraffic
DOIs
StatePublished - Jan 1 2019

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Endoplasmic Reticulum
Neurons
Spinocerebellar Ataxias
Drosophila
Caenorhabditis elegans
Torpedo
Neurodegenerative diseases
Embryonic Structures
RNA-Binding Proteins
Axons
Ataxin-2
Purkinje Cells
Diptera
Neurodegenerative Diseases
Cerebellum
Oocytes
Embryonic Development
Phenotype

Keywords

  • Ataxin-2
  • ATX-2
  • cytokinesis
  • DAtx-2
  • endoplasmic reticulum
  • mitosis
  • neurons
  • RBPs
  • RNA

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

del Castillo, U., Gnazzo, M. M., Sorensen Turpin, C. G., Nguyen, K. C. Q., Semaya, E., Lam, Y., ... Skop, A. R. (2019). Conserved role for Ataxin-2 in mediating endoplasmic reticulum dynamics. Traffic. https://doi.org/10.1111/tra.12647

Conserved role for Ataxin-2 in mediating endoplasmic reticulum dynamics. / del Castillo, Urko; Gnazzo, Megan M.; Sorensen Turpin, Christopher G.; Nguyen, Ken C.Q.; Semaya, Emily; Lam, Yuwan; de Cruz, Matthew A.; Bembenek, Joshua N.; Hall, David H.; Riggs, Blake; Gelfand, Vladimir I.; Skop, Ahna R.

In: Traffic, 01.01.2019.

Research output: Contribution to journalArticle

del Castillo, U, Gnazzo, MM, Sorensen Turpin, CG, Nguyen, KCQ, Semaya, E, Lam, Y, de Cruz, MA, Bembenek, JN, Hall, DH, Riggs, B, Gelfand, VI & Skop, AR 2019, 'Conserved role for Ataxin-2 in mediating endoplasmic reticulum dynamics', Traffic. https://doi.org/10.1111/tra.12647
del Castillo U, Gnazzo MM, Sorensen Turpin CG, Nguyen KCQ, Semaya E, Lam Y et al. Conserved role for Ataxin-2 in mediating endoplasmic reticulum dynamics. Traffic. 2019 Jan 1. https://doi.org/10.1111/tra.12647
del Castillo, Urko ; Gnazzo, Megan M. ; Sorensen Turpin, Christopher G. ; Nguyen, Ken C.Q. ; Semaya, Emily ; Lam, Yuwan ; de Cruz, Matthew A. ; Bembenek, Joshua N. ; Hall, David H. ; Riggs, Blake ; Gelfand, Vladimir I. ; Skop, Ahna R. / Conserved role for Ataxin-2 in mediating endoplasmic reticulum dynamics. In: Traffic. 2019.
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AU - de Cruz, Matthew A.

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