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Rab35 controls cilium length, function and membrane composition.

Stefanie Kuhns1,2, Cecília Seixas3, Sara Pestana3

  • 1School of Biomolecular and Biomedical Science, University College Dublin, Dublin 4, Ireland.

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|August 22, 2019
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Summary
This summary is machine-generated.

Rab35 protein is crucial for primary cilia function and length, impacting Sonic hedgehog (Shh) signaling and ciliopathies. Its loss disrupts cilia and causes developmental defects, highlighting its role in cellular processes.

Keywords:
Arl13bRab35Smoothenedcilialeft-right asymmetry

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Background:

  • Rab and Arl guanine nucleotide-binding (G) proteins regulate trafficking pathways.
  • Primary cilia are sensory organelles critical for Sonic hedgehog (Shh) signaling and implicated in ciliopathies.
  • Rab35 is a known regulator of endocytic recycling, actin remodeling, and cytokinesis.

Purpose of the Study:

  • To investigate the role of Rab35 in the function, formation, and composition of primary cilia.
  • To determine if Rab35 regulates Shh signaling pathways within cilia.
  • To explore the impact of Rab35 on ciliogenesis and ciliary length.

Main Methods:

  • Utilized mammalian cell culture and zebrafish models (including knockout and morpholino knockdown).
  • Employing techniques such as siRNA, GFP-tagging, and co-immunoprecipitation to study protein localization and interactions.
  • Assessed ciliary length, ciliary membrane protein levels, and left-right asymmetry defects.

Main Results:

  • Rab35 loss significantly reduces primary cilium length in mammalian cells and zebrafish Kupffer's vesicle.
  • Rab35 deficiency leads to motile cilia-associated left-right asymmetry defects in zebrafish.
  • Rab35 regulates ciliary levels of Shh pathway components like Smoothened and Arl13b, and affects ciliary PI(4,5)P2 levels.

Conclusions:

  • Rab35 plays a significant role in regulating primary cilium length, membrane composition, and overall function.
  • Rab35 is implicated in pathways controlling ciliary levels of Shh signal regulators, suggesting a link to ciliopathies.
  • The study identifies novel ciliary functions for the multitasking Rab35 protein.