CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels
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CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels. / Gonçalves, André Brás; Hasselbalch, Sarah Kirstine; Joensen, Beinta Biskopstø; Patzke, Sebastian; Martens, Pernille; Ohlsen, Signe Krogh; Quinodoz, Mathieu; Nikopoulos, Konstantinos; Suleiman, Reem; Jeppesen, Magnus Per Damsø; Weiss, Catja; Christensen, Søren Tvorup; Rivolta, Carlo; Andersen, Jens S.; Farinelli, Pietro; Pedersen, Lotte Bang.
I: eLife, Bind 10, e63731, 2021.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - CEP78 functions downstream of CEP350 to control biogenesis of primary cilia by negatively regulating CP110 levels
AU - Gonçalves, André Brás
AU - Hasselbalch, Sarah Kirstine
AU - Joensen, Beinta Biskopstø
AU - Patzke, Sebastian
AU - Martens, Pernille
AU - Ohlsen, Signe Krogh
AU - Quinodoz, Mathieu
AU - Nikopoulos, Konstantinos
AU - Suleiman, Reem
AU - Jeppesen, Magnus Per Damsø
AU - Weiss, Catja
AU - Christensen, Søren Tvorup
AU - Rivolta, Carlo
AU - Andersen, Jens S.
AU - Farinelli, Pietro
AU - Pedersen, Lotte Bang
PY - 2021
Y1 - 2021
N2 - CEP78 is a centrosomal protein implicated in ciliogenesis and ciliary length control, and mutations in the CEP78 gene cause retinal cone-rod dystrophy associated with hearing loss. However, the mechanism by which CEP78 affects cilia formation is unknown. Based on a recently discovered disease-causing CEP78 p.L150S mutation, we identified the disease-relevant interactome of CEP78. We confirmed that CEP78 interacts with the EDD1-DYRK2-DDB1VPRBP E3 ubiquitin ligase complex, which is involved in CP110 ubiquitination and degradation, and identified a novel interaction between CEP78 and CEP350 that is weakened by the CEP78L150S mutation. We show that CEP350 promotes centrosomal recruitment and stability of CEP78, which in turn leads to centrosomal recruitment of EDD1. Consistently, cells lacking CEP78 display significantly increased cellular and centrosomal levels of CP110, and depletion of CP110 in CEP78-deficient cells restored ciliation frequency to normal. We propose that CEP78 functions downstream of CEP350 to promote ciliogenesis by negatively regulating CP110 levels via an EDD1-dependent mechanism.
AB - CEP78 is a centrosomal protein implicated in ciliogenesis and ciliary length control, and mutations in the CEP78 gene cause retinal cone-rod dystrophy associated with hearing loss. However, the mechanism by which CEP78 affects cilia formation is unknown. Based on a recently discovered disease-causing CEP78 p.L150S mutation, we identified the disease-relevant interactome of CEP78. We confirmed that CEP78 interacts with the EDD1-DYRK2-DDB1VPRBP E3 ubiquitin ligase complex, which is involved in CP110 ubiquitination and degradation, and identified a novel interaction between CEP78 and CEP350 that is weakened by the CEP78L150S mutation. We show that CEP350 promotes centrosomal recruitment and stability of CEP78, which in turn leads to centrosomal recruitment of EDD1. Consistently, cells lacking CEP78 display significantly increased cellular and centrosomal levels of CP110, and depletion of CP110 in CEP78-deficient cells restored ciliation frequency to normal. We propose that CEP78 functions downstream of CEP350 to promote ciliogenesis by negatively regulating CP110 levels via an EDD1-dependent mechanism.
U2 - 10.7554/elife.63731
DO - 10.7554/elife.63731
M3 - Journal article
C2 - 34259627
VL - 10
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e63731
ER -
ID: 276379904