CCDC61/VFL3 Is a Paralog of SAS6 and Promotes Ciliary Functions

Area of Science:

• Cell Biology
• Structural Biology
• Biochemistry

Background:

• Centrioles exhibit 9-fold rotational symmetry, scaffolded by SAS6.
• Centriole-associated structures, like Chlamydomonas striated fibers, can break this symmetry and are vital for ciliary function.
• The protein CCDC61/VFL3's role in this process is not fully understood.

Purpose of the Study:

• To elucidate the structural and functional role of CCDC61 in centriole-associated structures.
• To investigate the relationship between CCDC61 and SAS6.

Main Methods:

• X-ray crystallography to determine CCDC61 structure.
• Biochemical assays to assess microtubule binding.
• Functional analysis in Chlamydomonas.

Main Results:

• CCDC61 is a paralog of SAS6.
• CCDC61 forms linear filaments via two homodimerization interfaces, distinct from SAS6 rings.
• CCDC61 directly binds microtubules.
• Specific CCDC61 residues crucial for microtubule binding are essential for ciliary function in Chlamydomonas.

Conclusions:

• CCDC61 and SAS6 likely evolved from a shared ancestor, diverging to scaffold different basal body-associated structures.
• CCDC61's filament formation and microtubule binding are key to its role in ciliary function.