Biology subjects

Lince-Faria, M.

Publications and source records attributed to Lince-Faria, M..

3 recordsLinked to original sources

bioRxiv2023

The maintenance of centriole appendages and motile cilia basal body anchoring relies on TBCCD1

Centrosomes are organelles consisting of two structurally and functionally distinct centrioles, with the mother centriole having complex distal (DA) and subdistal appendages (SDA). Despite their importance, how appendages are assembled and maintained remains unclear. This study investigated human TBCCD1, a centrosomal protein essential for centrosome positioning, to uncover its localization and role at centrioles. We found that TBCCD1 localizes at both proximal and distal regions of the two centrioles, forming a complex structure spanning from SDA to DA and extending inside and outside the centriole lumen. TBCCD1 depletion caused centrosome mispositioning, which was partially rescued by taxol, and the loss of microtubules (MTs) anchored to centrosomes. TBCCD1 depletion also reduced levels of SDA proteins involved in MT anchoring such as Centriolin/CEP110, Ninein, and CEP170. Additionally, TBCCD1 was essential for the correct positioning of motile cilia basal bodies and associated structures in Paramecium. This study reveals that TBCCD1 is an evolutionarily conserved protein essential for centriole and basal body localization and appendage assembly and maintenance. A BioID screening also linked TBCCD1 to ciliopathy-associated protein networks.

cell biology↗

bioRxiv2022

Ana1/CEP295 is an essential player in the centrosome maintenance program regulated by Polo kinase

Centrioles play critical roles in our cells, being part of centrosomes and cilia, which are important microtubule organising centers (MTOC) with a variety of roles. While centrioles are very stable structures, they disappear in certain cell types upon differentiation, such as in oocytes. Little is known about the regulation of centriole structural integrity. We previously uncovered that the pericentriolar material (PCM), and its recruiter Polo kinase, are required for both the maintenance of centriole structural integrity and centrosome MTOC activity. Using an hypothesis driven RNAi screen, we show that both the cartwheel and the centriole wall play an important role in centrosome integrity. In particular, we uncovered that the centriole wall protein ANA1 is critical for the integrity of both new and mature centrioles, in Drosophila oogenesis as well as in cultured cells. Moreover, our results show that the activity of both Polo and the PCM in centriole integrity depends on ANA1. Our work suggests that the structural integrity of centrioles, once thought to be very stable organelles, depends on the turnover of key components, suggesting new perspectives for understanding the dysfunction of those structures in disease.

cell biology↗

bioRxiv2021

Myosin VI regulates ciliogenesis by promoting the turnover of the centrosomal/satellite protein OFD1

The actin motor protein myosin VI is a multivalent protein with diverse functions. Here, we identified and characterised a myosin VI ubiquitous interactor, the oral-facial-digital syndrome 1 (OFD1) protein, whose mutations cause malformations of the face, oral cavity, digits, and polycystic kidney disease. We found that myosin VI regulates the localisation of OFD1 at the centrioles and, as a consequence, the recruitment of the distal appendage protein cep164. Myosin VI depletion in non-tumoural cell lines causes an aberrant localisation of OFD1 along the centriolar walls, which is due to a reduction in the OFD1 mobile fraction. Finally, loss of myosin VI triggers a severe defect in ciliogenesis that could be causally linked to an impairment in the autophagic removal of OFD1 from satellites. Altogether, our results highlight an unprecedent layer of regulation of OFD1 and a pivotal role of myosin VI in coordinating the formation of the distal appendages and primary cilium with important implications for the genetic disorders known as ciliopathies.

cell biology↗