The microtubule-associated proteins CKAP2 and its paralog CKAP2-Like control ciliogenesis in human cells

Ciliogenesis is a fundamental cellular process that develops cilia, and it depends on microtubule-associated proteins (MAPs) to control the dynamics of axonemal microtubules. When these MAPs are misregulated, they can disturb ciliary balance, leading to various ciliopathies. CKAP2 and CKAP2-Like, two MAPs, are not only involved in regulating microtubule dynamics during cell division but also are found in ciliary organelles.

While CKAP2 overexpression can cause chromosomal instability and cancer, CKAP2-Like deficiency leads to a developmental disorder called Filippi syndrome, which shares qualities with ciliopathies. However, the exact roles of these MAPs at primary cilia are not well understood. This study reveals that both CKAP2 and CKAP2-Like are components of axonemal components in motile and primary cilia of human cells.

It is noted that CKAP2-positive cilia are connected to cell cycle progression, and the common microtubule-binding domain of CKAP2, which is crucial for microtubule polymerization and stabilization, is necessary for its ciliary localization. Interestingly, losing either of these MAPs results in longer cilia without affecting ciliogenesis, leading to a higher concentration of the surviving MAP at the ciliary tip and impaired Gli2 accumulation.

Conversely, when both MAPs are deleted simultaneously, ciliogenesis is suppressed, but there is little change in ciliary length compared to the wild-type. This research shows that CKAP2 and CKAP2-Like are axonemal MAPs that help with ciliogenesis, partly compensating for each other in human cells.