Mark Van Breugel: Architecture and Mechanism of the CBY1–FAM92A Ciliogenesis Complex

Speaker:  Dr. Mark Van Breugel
Queen Mary University of London

School of Biological & Behavioural Sciences

Host:       Oliver Daumke

Abstract:

Architecture and Mechanism of the CBY1–FAM92A Ciliogenesis Complex

The formation of cilia involves the coordinated binding, fusion, and remodelling of lipid membranes at the distal end of centriole-derived basal bodies, yet the mechanisms governing this process remain incompletely understood. The CBY1–FAM92A complex is a membrane-binding protein module that localises to the distal end of centrioles/basal bodies and is required for ciliogenesis, although the mechanistic details of its function and its precise role in early cilia formation are not fully established. Using integrated cell biological, biochemical, and structural analyses, we show that this complex tubulates membranes through coat formation and selectively associates with phosphoinositide-rich plasma membranes. Mechanistically, CBY1 enhances FAM92A membrane binding via a segment that is critical for efficient ciliogenesis. Loss of the CBY1–FAM92A complex results in early-stage arrest of ciliogenesis, accompanied by defects in membrane association of basal bodies. These findings establish a mechanistic framework for CBY1–FAM92A function, highlight its role in orchestrating membrane dynamics during early ciliogenesis and offer a foundation for understanding how membrane remodelling is integrated with the broader machinery of ciliogenesis.