We are pleased to share our latest collaborative article, published in the Journal of Cell Biology.
Alström syndrome is a rare human ciliopathy caused by mutations in ALMS1, yet how this protein contributes to cilia function has long been unclear. Unlike most ciliopathy-associated proteins, which act at the cilium or its base, ALMS1 localizes to the proximal end of centrioles — raising the possibility that it supports cilia through a distinct mechanism.
In this study we find that, without ALMS1, centrioles are short and frequently break at their proximal ends. These truncated, broken centrioles display reduced microtubule-organizing activity and disrupted centriole linkers. As a consequence, Golgi-derived cargos — including transmembrane components of the transition zone — are no longer efficiently trafficked to the centrosome. ALMS1 is therefore required for transition zone assembly, ciliogenesis, and the control of ciliary membrane composition.
In mice, disruption of ALMS1 causes a progressive, age-dependent loss of cilia in tissues affected in Alström syndrome, including the retina, kidney and brain. Together, these findings suggest that Alström syndrome arises from a loss of proximal centriole integrity and centrosome-directed protein trafficking, which compromises both the assembly and the maintenance of cilia.
This work was led by Thao P. Phan in the laboratory of Jeremy F. Reiter at the University of California, San Francisco, to whom the main credit for this project belongs. Our contribution was the transmission electron microscopy analysis of centriole and cilia ultrastructure. It has been a real pleasure to work with Thao, first author of the paper, and we are truly grateful to Thao and Jeremy for involving us in this work, which continues a long and fruitful collaboration with the Reiter lab.
Reference
Phan TP, Derderian C, Herranz-Pérez V, Li KH, Burlingame AL, Reiter JF. ALMS1 stabilizes the proximal centriole to drive transition zone assembly and ciliogenesis. Journal of Cell Biology 226(1), e202605019 (2026). DOI: https://doi.org/10.1083/jcb.202605019