A Short CEP135 Splice Isoform Controls Centriole Duplication.

Area of Science:

• Cell Biology
• Molecular Biology
• Genetics

Background:

• Centriole duplication ensures one round per cell cycle, preventing defects like supernumerary centrosomes and altered ciliary signaling.
• Centriole assembly relies on regulated protein levels, localization, and modifications, initiated by cartwheel structure formation involving SAS-6.
• CEP135 is crucial for linking SAS-6 and CPAP in microtubule nucleation and triplet formation.

Purpose of the Study:

• To investigate the role of CEP135 protein isoforms in regulating centriole duplication.
• To elucidate the mechanism by which CEP135 isoforms modulate centriole assembly and cell cycle progression.

Main Methods:

• Identification and characterization of two CEP135 protein isoforms: CEP135(full) and CEP135(mini).
• Analysis of the localization and function of CEP135 isoforms during the cell cycle using centrosomal markers.
• Investigating the impact of CEP135 isoforms on the localization of SAS-6, CPAP, and γ-tubulin.

Main Results:

• Two antagonistic CEP135 isoforms were identified: CEP135(full) promotes centriole assembly, while CEP135(mini) represses it.
• CEP135(mini) inhibits duplication by limiting the centrosomal localization of SAS-6, CPAP, and γ-tubulin.
• CEP135 isoforms display distinct cell cycle-dependent centrosomal localization, with CEP135(mini) decreasing at anaphase onset.

Conclusions:

• A novel mechanism for limiting centriole duplication involves a splice isoform (CEP135(mini)) that represses assembly.
• The decrease of CEP135(mini) at anaphase onset likely facilitates new centriole assembly.
• Differential regulation of CEP135 isoforms provides precise control over centriole duplication.