TY - JOUR
T1 - Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication
AU - Kodani, Andrew
AU - Yu, Timothy W.
AU - Johnson, Jeffrey R.
AU - Jayaraman, Divya
AU - Johnson, Tasha L.
AU - Al-Gazali, Lihadh
AU - Sztriha, Laszló
AU - Partlow, Jennifer N.
AU - Kim, Hanjun
AU - Krup, Alexis L.
AU - Dammermann, Alexander
AU - Krogan, Nevan J.
AU - Walsh, Christopher A.
AU - Reiter, Jeremy F.
N1 - Publisher Copyright:
© Kodani et al.
PY - 2015/8/22
Y1 - 2015/8/22
N2 - Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. Thus, centriolar satellites build a MCPH complex critical for human neurodevelopment that promotes CDK2 centrosomal localization and centriole duplication.
AB - Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. Thus, centriolar satellites build a MCPH complex critical for human neurodevelopment that promotes CDK2 centrosomal localization and centriole duplication.
UR - http://www.scopus.com/inward/record.url?scp=84941913904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84941913904&partnerID=8YFLogxK
U2 - 10.7554/eLife.07519
DO - 10.7554/eLife.07519
M3 - Article
C2 - 26297806
AN - SCOPUS:84941913904
SN - 2050-084X
VL - 4
JO - eLife
JF - eLife
IS - AUGUST2015
M1 - e07519
ER -