Microcephaly: STIL(l) a Tale of Too Many Centrosomes
نویسندگان
چکیده
Centrosome mutations associated with microcephaly are normally thought to result in loss-of-function phenotypes. A new study shows, however, that mutations found in the human microcephaly STIL gene cause centrosome amplification, suggesting a direct link between the presence of extra centrosomes and the establishment of this disease.
منابع مشابه
STIL Microcephaly Mutations Interfere with APC/C-Mediated Degradation and Cause Centriole Amplification
BACKGROUND STIL is a centriole duplication factor that localizes to the procentriolar cartwheel region, and mutations in STIL are associated with autosomal recessive primary microcephaly (MCPH). Excess STIL triggers centriole amplification, raising the question of how STIL levels are regulated. RESULTS Using fluorescence time-lapse imaging, we identified a two-step process that culminates in ...
متن کاملCrystal structures of the CPAP/STIL complex reveal its role in centriole assembly and human microcephaly
Centrioles organise centrosomes and template cilia and flagella. Several centriole and centrosome proteins have been linked to microcephaly (MCPH), a neuro-developmental disease associated with small brain size. CPAP (MCPH6) and STIL (MCPH7) are required for centriole assembly, but it is unclear how mutations in them lead to microcephaly. We show that the TCP domain of CPAP constitutes a novel ...
متن کاملQuantitative analysis of human centrosome architecture by targeted proteomics and fluorescence imaging
Centrioles are essential for the formation of centrosomes and cilia. While numerical and/or structural centrosomes aberrations are implicated in cancer, mutations in centriolar and centrosomal proteins are genetically linked to ciliopathies, microcephaly, and dwarfism. The evolutionarily conserved mechanisms underlying centrosome biogenesis are centered on a set of key proteins, including Plk4,...
متن کاملSTIL is required for centriole duplication in human cells.
Centrioles are key structural elements of centrosomes and primary cilia. In mammals, only a few proteins including PLK4, CPAP (CENPJ), SAS6, CEP192, CEP152 and CEP135 have thus far been identified to be required for centriole duplication. STIL (SCL/TAL1 interrupting locus, also known as SIL) is a centrosomal protein that is essential for mouse and zebrafish embryonic development and mutated in ...
متن کاملA Tale of Too Many Centrosomes
Having the correct number of centrosomes is crucial for proper chromosome segregation during cell division and for the prevention of aneuploidy, a hallmark of many cancer cells. Several recent studies (Basto et al., 2008; Kwon et al., 2008; Yang et al., 2008) reveal the importance of mechanisms that protect against the consequences of harboring too many centrosomes.
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ورودعنوان ژورنال:
- Current Biology
دوره 24 شماره
صفحات -
تاریخ انتشار 2014