期刊
JOURNAL OF CELL BIOLOGY
卷 220, 期 9, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.202011133
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资金
- National Institutes of Health [R01HD089918, R01R01DE029454, R01AR054396, K99GM126136/R00GM126136, R01GM124334]
- Valencian Council for Innovation, Universities, Science and Digital Society [PROMETEO/2019/075]
- Spanish Ministry of Science, Innovation and Universities [PCI2018-093062]
- University of California, San Francisco Mary Anne Koda-Kimble Seed Award for Innovation
- Jane Coffin Childs Memorial Fund for Medical Research postdoctoral fellowship
- Program for Breakthrough Biomedical Research Award - Sandler Foundation
A module called DISCO was discovered, which supports ciliogenesis by limiting centriole length and assembling distal appendages on the distal centriole. Lack of DISCO components CEP90 or MNR results in the inability to generate cilia and assemble distal appendages.
Cells inherit two centrioles, the older of which is uniquely capable of generating a cilium. Using proteomics and superresolved imaging, we identify a module that we term DISCO (distal centriole complex). The DISCO components CEP90, MNR, and OFD1 underlie human ciliopathies. This complex localizes to both distal centrioles and centriolar satellites, proteinaceous granules surrounding centrioles. Cells and mice lacking CEP90 or MNR do not generate cilia, fail to assemble distal appendages, and do not transduce Hedgehog signals. Disrupting the satellite pools does not affect distal appendage assembly, indicating that it is the centriolar populations of MNR and CEP90 that are critical for ciliogenesis. CEP90 recruits the most proximal known distal appendage component, CEP83, to root distal appendage formation, an early step in ciliogenesis. In addition, MNR, but not CEP90, restricts centriolar length by recruiting OFD1. We conclude that DISCO acts at the distal centriole to support ciliogenesis by restraining centriole length and assembling distal appendages, defects in which cause human ciliopathies.
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