Biology subjects

De Freitas, S.

Publications and source records attributed to De Freitas, S..

3 recordsLinked to original sources

bioRxiv2026

Cfap410a and Cby work together with tissue-specific requirements to build Drosophila ciliary transition zones

Cilia and flagella perform essential physiological functions in eukaryotes, and defects in these organelles cause several human diseases, including cancer and ciliopathies. The architecture of cilia is highly organized. The ciliary compartment is separated from the cytoplasm by the transition zone (TZ). The severity of ciliopathies linked to TZ assembly defects highlights the TZ's critical role. Although several core conserved complexes are involved in TZ assembly, variations in TZ composition are associated with structurally and functionally diverse cilia. Here, we identify Cfap410a as a novel component of the ciliary TZ in the two Drosophila ciliated tissues, male germ cells and sensory neurons. Cfap410a is one of the two Drosophila paralogs (Cfap410a and Cfap410b) of human CFAP410, whose mutations are associated with axial spondylo-metaphyseal dysplasia, retinitis pigmentosa and amyotrophic lateral sclerosis. We show here that Cfap410a is a proximity partner of Cby and that they act cooperatively in the hierarchy of the TZ assembly program by bridging the CEP290 and MKS transition zone modules. Simultaneous loss of Cfap410a and Cby halts ciliary growth by disrupting TZ formation in multiple types of Drosophila ciliated cells, each of which exhibiting varying dependence on these two proteins. Interestingly, the function of Cfap410a and Cfap410b are not functionally redundant, indicating that the two proteins have evolved towards specific functions. In summary, our results propose a novel role for CFAP410a at the TZ and provide an explanation for how deregulation of conserved TZ components could lead to tissue-specific ciliopathies.

cell biology↗

bioRxiv2026

ALMS1 contributes to centriole proximal architecture and stability

Centrioles are highly organised microtubular scaffolds which grow and mature progressively during successive cell cycles. Their molecular organisation is extensively characterized, yet the contribution of several components to centriole assembly, maturation or stability is incompletely understood. Here, using ultrastructure expansion microscopy and transmission electron microscopy, we show that ALMS1, the protein mutated in Alstrom syndrome, is required for proper centriole architecture. In absence of ALMS1, RPE1 cells exhibit shorter centrioles with defects in the microtubular wall, including broken or missing triplets or open B/C tubules. These structural defects arise after procentriole assembly. We show that ALMS1 loss selectively reduces the proximal region proteins CCDC77 and CEP44, leaving intact central and distal ones. ALMS1 is further required for the recruitment of the proximal CEP135 cap and the clearance of the {gamma}-tubulin/GCP2 pool present at the procentriole base. Our findings thus identify ALMS1 as a key organiser of the centriole proximal domain and required for remodelling and stabilising the proximal end of centrioles during cell cycle progression.

cell biology↗

bioRxiv2025

Estradiol promotes habituation learning via an unidentified target, bypassing the suppressive effects of established Estrogen Receptors

Habituating to the constant stimuli in the environment is a critical learning process conserved across species. We use a larval zebrafish visual response to sudden darkness as a model for studying habituation learning, where zebrafish reduce their responses to repeated stimulations. In this paradigm, treatment with estradiol strongly increases learning rate, resulting in more strongly suppressed responses. We used mutant lines for the Estrogen Receptors (esr1, esr2a, esr2b, gper1) in an attempt to identify the receptor(s) mediating these effects. These experiments failed to identify a necessary receptor (or combination of receptors). Surprisingly, esr1, esr2a, and gper1 mutants showed weak but consistent increases in habituation, indicating these receptors suppress habituation learning. These experiments demonstrate that estradiol is a complex modulator of learning in our model, where the learning-promoting effects are mediated by an unidentified estradiol target, and the classical Estrogen Receptors act in competition to subtly suppress learning.

neuroscience↗