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A ciliopathy complex restrains centriolar length and builds distal appendages to initiate ciliogenesis.

ABSTRACT: Mitosis segregates into each daughter cell two centrioles, the older of which is uniquely capable of generating a cilium. How this older centriole, called the mother centriole, initiates ciliogenesis remains poorly understood. We have identified an evolutionarily conserved complex comprised of CEP90, OFD1, MNR and FOPNL. Human mutations in CEP90, MNR and OFD1 cause ciliopathies. Super-resolution microscopy revealed that this complex forms a ring at the distal centriole. Centrioles of cells lacking MNR or CEP90 failed to assemble distal appendages and cannot generate cilia. In addition to the centrioles, complex members localized to centriolar satellites, proteinaceous granules surrounding the centrioles. Disruption of satellites did not affect distal appendage assembly, indicating that the centriolar pool is required for ciliogenesis. Consistent with an essential role in ciliogenesis, mice lacking MNR or CEP90 did not assemble cilia, did not survive beyond embryonic day 9.5, and did not transduce Hedgehog signals. In addition to ciliogenesis, MNR, but not CEP90, restrained centriolar length. MNR recruited both OFD1, required for centriolar length control, and CEP90, which recruits CEP83 to root distal appendages. Thus, an evolutionarily conserved ciliopathy-associated complex functions at the distal centriole to control centriole length and assemble distal appendages.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Danielle Swaney

LAB HEAD: Nevan Krogan

PROVIDER: PXD022372 | Pride | 2021-06-15

REPOSITORIES: Pride

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