MiniBAR/GARRE1 is a dual Rac and Rab effector required for ciliogenesis
Murielle P Serres1, Ronan Shaughnessy1, Sophie Escot2
1Institut Pasteur, Université de Paris, CNRS UMR3691, Membrane Traffic and Cell Division Laboratory, 25-28 rue du Dr Roux, 75015 Paris, France.
Developmental Cell
|October 24, 2023
Summary
MiniBAR protein controls cell structure and transport for cilia formation. Its depletion causes short cilia and developmental defects, highlighting its crucial role in ciliogenesis and preventing ciliopathies.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Cilia are vital for cell signaling, sensing, and development.
- Cilia formation (ciliogenesis) requires reduced actin contractility and proper intracellular trafficking.
- Coordination between these processes during ciliogenesis remains poorly understood.
Purpose of the Study:
- To identify and characterize a novel protein involved in coordinating actin cytoskeleton dynamics and membrane trafficking for ciliogenesis.
- To elucidate the molecular mechanism by which this protein regulates ciliogenesis.
Main Methods:
- Protein identification and characterization (MiniBAR, Rac1, Rab35).
- Localization studies using microscopy.
- Functional assays involving protein depletion in cell culture and zebrafish models.
- Analysis of actin cytoskeleton organization, contractility, and protein trafficking (IFT88, ARL13B).
Main Results:
- A novel protein, MiniBAR (truncated BAR domain protein), was identified and binds Rac1 and Rab35.
- MiniBAR localizes to the plasma membrane and intracellular vesicles, with dynamic pulsing at the ciliary membrane.
- MiniBAR depletion results in shortened cilia due to altered Rac/Rho GTPase levels, increased acto-myosin contractility, and impaired IFT88/ARL13B trafficking.
- Zebrafish embryos with depleted MiniBAR exhibit short cilia and ciliopathy-like symptoms, including left-right asymmetry defects.
Conclusions:
- MiniBAR acts as a dual effector for Rac and Rab GTPases.
- It integrates regulation of the actin cytoskeleton and membrane trafficking pathways essential for ciliogenesis.
- MiniBAR dysfunction contributes to ciliopathies, underscoring its critical role in cilia formation and function.
Keywords:
BAR domainRab GTPaseRab35Rac GTPaseactin cytoskeletonciliogenesisciliopathiesmembrane traffickingmyosin IIMore Related Videos
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