TY - JOUR
T1 - SFI1 promotes centriole duplication by recruiting USP9X to stabilize the microcephaly protein STIL
AU - Kodani, Andrew
AU - Moyer, Tyler
AU - Chen, Allen
AU - Holland, Andrew
AU - Walsh, Christopher A.
AU - Reiter, Jeremy F.
N1 - Publisher Copyright:
© 2019 Kodani et al. This article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
PY - 2019
Y1 - 2019
N2 - In mammals, centrioles participate in brain development, and human mutations affecting centriole duplication cause microcephaly. Here, we identify a role for the mammalian homologue of yeast SFI1, involved in the duplication of the yeast spindle pole body, as a critical regulator of centriole duplication in mammalian cells. Mammalian SFI1 interacts with USP9X, a deubiquitylase associated with human syndromic mental retardation. SFI1 localizes USP9X to the centrosome during S phase to deubiquitylate STIL, a critical regulator of centriole duplication. USP9X-mediated deubiquitylation protects STIL from degradation. Consistent with a role for USP9X in stabilizing STIL, cells from patients with USP9X loss-of-function mutations have reduced STIL levels. Together, these results demonstrate that SFI1 is a centrosomal protein that localizes USP9X to the centrosome to stabilize STIL and promote centriole duplication. We propose that the USP9X protection of STIL to facilitate centriole duplication underlies roles of both proteins in human neurodevelopment.
AB - In mammals, centrioles participate in brain development, and human mutations affecting centriole duplication cause microcephaly. Here, we identify a role for the mammalian homologue of yeast SFI1, involved in the duplication of the yeast spindle pole body, as a critical regulator of centriole duplication in mammalian cells. Mammalian SFI1 interacts with USP9X, a deubiquitylase associated with human syndromic mental retardation. SFI1 localizes USP9X to the centrosome during S phase to deubiquitylate STIL, a critical regulator of centriole duplication. USP9X-mediated deubiquitylation protects STIL from degradation. Consistent with a role for USP9X in stabilizing STIL, cells from patients with USP9X loss-of-function mutations have reduced STIL levels. Together, these results demonstrate that SFI1 is a centrosomal protein that localizes USP9X to the centrosome to stabilize STIL and promote centriole duplication. We propose that the USP9X protection of STIL to facilitate centriole duplication underlies roles of both proteins in human neurodevelopment.
UR - http://www.scopus.com/inward/record.url?scp=85069266700&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85069266700&partnerID=8YFLogxK
U2 - 10.1083/jcb.201803041
DO - 10.1083/jcb.201803041
M3 - Article
C2 - 31197030
AN - SCOPUS:85069266700
SN - 0021-9525
VL - 218
SP - 2185
EP - 2197
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 7
ER -