Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comment
. 2018 Nov 1;141(11):e78.
doi: 10.1093/brain/awy258.

PLD3 and spinocerebellar ataxia

Adriana Carolina Gonzalez  1 , Stijn Stroobants  2 , Pia Reisdorf  1 , Amanda Lee Gavin  3 , David Nemazee  3 , Dominik Schwudke  4 , Rudi D'Hooge  2 , Paul Saftig  1 , Markus Damme  1
Affiliations
Comment

PLD3 and spinocerebellar ataxia

Adriana Carolina Gonzalez et al. Brain. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Impaired lysosomal delivery, proteolytic processing and loss of function of the PLD3-L308P mutation. (A) Confocal microscopy of HeLa cells transfected with the PLD3-WT or PLD3-L308P mutation followed by staining with the indicated antibodies. Pearson correlation coefficient (PCC) for co-localization for the indicated antibodies is depicted; n = 12 cells. (B) Immunoblot of PLD3-WT or PLD3-L308P mutation with indicated PLD3-specific antibodies and GAPDH. Quantification of the fragments relative to full-length protein is shown. UT = untransfected. (C) Ethidium-bromide stained polyacrylamide gel analysis of untreated ssDNA substrate and treated with untransfected HeLa cell lysates or transfected with PLD3-WT or PLD3-L308P-mutation transfected HeLa cell lysates. Quantification represents n = 3. ***P < 0.001; ns = not significant.
Figure 2
Figure 2
PLD3 expression in the cerebellum is low and PLD3 KO mice do not show any signs of cerebellar degeneration. (A) Immunoblot analysis of PLD3 expression in different brain regions of adult wild-type mice with an antibody against the N-terminus of PLD3; n = 3. (B) Targeting vector for PLD3 LacZ reporter and PLD3 KO mice. (C) β-Galactosidase activity in different brain regions of an adult PLD3-reporter mouse with X-Gal as colorimetric substrate. (D) Immunoblot analysis of brain lysates with an antibody against the N-terminus of PLD3. (E) Photograph of the brain of wild-type and PLD3 KO mice, 20 months old. (F) Calbindin-immunofluorescence of the cerebellum of a wild-type and a PLD3 KO mouse, 20 months old. (G) Immunofluorescence staining for calbindin (red), GFAP (green) of the molecular layer in lobule IV of 20-month-old wild-type and PLD3 KO mice. Nuclei are stained with DAPI (blue). (H) Rotarod latency in 5- and 9-month-old animals (n = 9–11).
See this image and copyright information in PMC

Comment in

Comment on

References

    1. Gavin AL,, Huang D,, Huber C,, Martensson A,, Tardif V,, Skog PD, et al. PLD3 and PLD4 are single-stranded acid exonucleases that regulate endosomal nucleic-acid sensing. Nat Immunol 2018; 19: 942–53. - PMC - PubMed
    1. Gonzalez AC,, Schweizer M,, Jagdmann S,, Bernreuther C,, Reinheckel T,, Saftig P, et al. Unconventional trafficking of mammalian phospholipase D3 to lysosomes. Cell Rep 2018; 22: 1040–53. - PubMed
    1. Nibbeling EAR,, Duarri A,, Verschuuren-Bemelmans CC,, Fokkens MR,, Karjalainen JM,, Smeets C, et al. Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia. Brain 2017; 140: 2860–78. - PubMed
    1. Pedersen KM,, Finsen B,, Celis JE,, Jensen NA. Expression of a novel murine phospholipase D homolog coincides with late neuronal development in the forebrain. J Biol Chem 1998; 273: 31494–504. - PubMed