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Advisor(s)
Abstract(s)
Cilia are microtubule-based organelles that protrude from the cell surface and fulfill critical motility and sensory functions being required for normal embryonic development and for homeostasis of human adult tissues. Cilia loss or dysfunction is associated with human ciliopathies. At their base cilia have a centriole/basal body (BB), which can be derived from the centrosome and assembles the ciliary axoneme. This process requires the correct positioning/anchoring of the centrosome’s mother centriole/BB to the cell membrane. A clear picture of the different signals and players involved in centrosome positioning/anchoring is still not available. Published work from our group identified a new centrosomal TBCC domain-containing human protein (TBCCD1) that is involved in centrosome correct positioning and primary cilia assembly. In mammalian cells, TBCCD1 is observed at pericentriolar satellites, in basal bodies of primary and motile cilia and at primary cilia ciliopathy hot domain, the transition zone. Super-resolution microscopy shows that TBCCD1 is localized at the distal region of the centrosome and its depletion dramatically affects the centrosome subdistal protein CEP170, a component of primary and motile cilia basal feet. By doing a proximity-dependent biotin identification (BioID-MS) screen for TBCCD1 interactors several well-known proteins encoded by ciliopathy genes were identified, e.g. the centrosomal proteins OFD1 and Moonraker/KIAA0753 associated with Digital Syndrome 1 and Joubert syndrome, respectively. OFD1 and Moonraker are required for the maintenance of centrosome structure and both proteins localization is dramatically disturbed by TBCCD1 depletion. To clarify the role of human TBCCD1 in cilia biogenesis we used the ciliate Paramecium. Noteworthy, in Paramecium TBCCD1 knockdown causes abnormal basal body associated rootlets organization, anomalous BB positioning/anchoring defects. Our data using human cells and the ciliate Paramecium support a role of TBCCD1 in centrosome structure maintenance and BB anchoring at the cell membrane. The Paramecium phenotypes confirm that TBCCD1 is a new candidate to a ciliopathic gene probably by founding the TBCCD1/Moonraker/OFD1 functional conserved module required for cilia assembly.
Description
Keywords
Centrosomal microtubule TBCCD1 Ciliate Paramecium Ciliopathic gene
Citation
Carmona B, Camelo C, Mehraz M, Lemullois M, Nolasco S, Soares H, et al. From centrosomal microtubule anchoring and organization to basal body positioning: TBCCD1 an elusive protein. In: VIII European Congress of Protistology – ISOP Joint Meeting, Rome (Italy), 28th July to 2nd August 2019. p. 55.