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Visualizing the Actin and Microtubule Cytoskeletons at the B-cell Immune Synapse Using Stimulated Emission Depletion STED Microscopy
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BBSome-deficient cells activate intraciliary CDC42 to trigger actin-dependent ciliary ectocytosis
Avishek Prasai1,2,3, Olha Ivashchenko1,2, Kristyna Maskova1
1Laboratory of Adaptive Immunity, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
EMBO Reports
|November 26, 2024
Summary
Bardet-Biedl syndrome (BBS) involves cilia dysfunction. Our study shows ciliary CDC42 triggers actin polymerization and ectocytosis in BBS cells, potentially worsening disease severity.
Area of Science:
- Cell Biology
- Genetics
- Biochemistry
Background:
- Bardet-Biedl syndrome (BBS) is a ciliopathy linked to BBSome dysfunction, affecting transmembrane receptor transport.
- Actin-dependent ectocytosis is a proposed compensatory mechanism for cargo retrieval defects in cilia, but its molecular basis in BBS is unclear.
Purpose of the Study:
- To investigate the regulation of actin polymerization and ectocytosis within cilia.
- To elucidate the role of ciliary CDC42 in BBS pathology.
Main Methods:
- Studied actin polymerization and ectocytosis in BBSome-deficient cells.
- Utilized CDC42 inhibition and Sonic Hedgehog pathway activation.
- Monitored G protein coupled receptor 161 (GPR161) localization.
Main Results:
- Ciliary CDC42, a RHO-family GTPase, was found to trigger actin polymerization, ectocytosis, and cilia shortening in BBSome-deficient cells.
- Sonic Hedgehog pathway activation specifically enhanced CDC42 activity in BBSome-deficient cilia.
- CDC42 inhibition reduced ciliary actin polymerization, leading to GPR161 accumulation in bulges during Sonic Hedgehog signaling.
Conclusions:
- Identified ciliary CDC42 as a key trigger for ciliary ectocytosis.
- Hyperactive ciliary CDC42 and ectocytosis may contribute to BBS disease severity through loss of ciliary material.
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