Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain

Shahzad S. Khan, Yuriko Sobu, View ORCID ProfileHerschel S. Dhekne, View ORCID ProfileFrancesca Tonelli, Kerryn Berndsen, View ORCID ProfileDario R. Alessi, View ORCID ProfileSuzanne R. Pfeffer
doi: https://doi.org/10.1101/2021.03.02.433576
Shahzad S. Khan
1Department of Biochemistry, Stanford University School of Medicine
3Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuriko Sobu
1Department of Biochemistry, Stanford University School of Medicine
3Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Herschel S. Dhekne
1Department of Biochemistry, Stanford University School of Medicine
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Herschel S. Dhekne
Francesca Tonelli
2MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee
3Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Francesca Tonelli
Kerryn Berndsen
2MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee
3Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dario R. Alessi
2MRC Protein Phosphorylation and Ubiquitylation Unit, University of Dundee
3Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Dario R. Alessi
Suzanne R. Pfeffer
1Department of Biochemistry, Stanford University School of Medicine
3Aligning Science Across Parkinson’s (ASAP) Collaborative Research Network, Chevy Chase, MD
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Suzanne R. Pfeffer
  • For correspondence: pfeffer@stanford.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Previously, we showed that cholinergic interneurons of the dorsal striatum lose cilia in mice harboring the Parkinson’s disease associated, kinase activating, R1441C LRRK2 mutation (Dhekne et al., 2018). Here we show that this phenotype is also seen in two mouse strains carrying the most common human G2019S LRRK2 mutation. Heterozygous loss of the PPM1H phosphatase that is specific for LRRK2-phosphorylated Rab GTPases (Berndsen et al., 2019) yields the same cilia loss phenotype, strongly supporting a connection between Rab GTPase phosphorylation and cilia loss. In addition, astrocytes throughout the striatum show a ciliation defect in LRRK2 and PPM1H-/+ mutant models. Hedgehog signaling requires cilia, and loss of cilia correlates here with a loss in induction of Hedgehog signaling as monitored by in situ hybridization of Gli1 transcripts. These data support a model in which LRRK2 and PPM1H mutant mice struggle to receive and respond to critical Hedgehog signals in the nigral-striatal pathway.

Copyright 
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 4.0 International license.
Back to top
PreviousNext
Posted March 02, 2021.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain
Shahzad S. Khan, Yuriko Sobu, Herschel S. Dhekne, Francesca Tonelli, Kerryn Berndsen, Dario R. Alessi, Suzanne R. Pfeffer
bioRxiv 2021.03.02.433576; doi: https://doi.org/10.1101/2021.03.02.433576
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Pathogenic LRRK2 control of primary cilia and Hedgehog signaling in neurons and astrocytes of mouse brain
Shahzad S. Khan, Yuriko Sobu, Herschel S. Dhekne, Francesca Tonelli, Kerryn Berndsen, Dario R. Alessi, Suzanne R. Pfeffer
bioRxiv 2021.03.02.433576; doi: https://doi.org/10.1101/2021.03.02.433576

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cell Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3691)
  • Biochemistry (7800)
  • Bioengineering (5678)
  • Bioinformatics (21295)
  • Biophysics (10584)
  • Cancer Biology (8179)
  • Cell Biology (11948)
  • Clinical Trials (138)
  • Developmental Biology (6764)
  • Ecology (10401)
  • Epidemiology (2065)
  • Evolutionary Biology (13875)
  • Genetics (9709)
  • Genomics (13075)
  • Immunology (8151)
  • Microbiology (20022)
  • Molecular Biology (7859)
  • Neuroscience (43073)
  • Paleontology (321)
  • Pathology (1279)
  • Pharmacology and Toxicology (2261)
  • Physiology (3353)
  • Plant Biology (7232)
  • Scientific Communication and Education (1314)
  • Synthetic Biology (2008)
  • Systems Biology (5539)
  • Zoology (1128)