CPAP is required for cilia formation in neuronal cells

Wu, Kuo-Sheng; Tang, Tang K.

doi:10.1242/bio.20121388

Cited by 23 publications

(27 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the finding that CriptÀ/À mice die at embryonic day 8 strongly suggests that it plays a more general developmental role and is consistent with the phenotypic consequence of knocking out other known PD disease genes, e.g., Cenpj and Pcnt (Wu and Tang 2012). Both patients with CRIPT homozygous truncation have a highly consistent and clinically recognizable phenotype of PD that is characterized by frontal bossing, high forehead, sparse hair and eyebrows, telecanthus, mild proptosis (staring look), upturned nostrils, and hypoplastic terminal phalanges with brachydactyly.…”

Section: Discussionsupporting

confidence: 62%

Genomic analysis of primordial dwarfism reveals novel disease genes

et al. 2014

View full text Add to dashboard Cite

Primordial dwarfism (PD) is a disease in which severely impaired fetal growth persists throughout postnatal development and results in stunted adult size. The condition is highly heterogeneous clinically, but the use of certain phenotypic aspects such as head circumference and facial appearance has proven helpful in defining clinical subgroups. In this study, we present the results of clinical and genomic characterization of 16 new patients in whom a broad definition of PD was used (e.g., 3M syndrome was included). We report a novel PD syndrome with distinct facies in two unrelated patients, each with a different homozygous truncating mutation in CRIPT. Our analysis also reveals, in addition to mutations in known PD disease genes, the first instance of biallelic truncating BRCA2 mutation causing PD with normal bone marrow analysis. In addition, we have identified a novel locus for Seckel syndrome based on a consanguineous multiplex family and identified a homozygous truncating mutation in DNA2 as the likely cause. An additional novel PD disease candidate gene XRCC4 was identified by autozygome/exome analysis, and the knockout mouse phenotype is highly compatible with PD. Thus, we add a number of novel genes to the growing list of PD-linked genes, including one which we show to be linked to a novel PD syndrome with a distinct facial appearance. PD is extremely heterogeneous genetically and clinically, and genomic tools are often required to reach a molecular diagnosis.

show abstract

Section: Discussionsupporting

confidence: 62%

Genomic analysis of primordial dwarfism reveals novel disease genes

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In summary, we report the identification of centrobin as an upstream regulator of CPAP, a centrosomal protein with crucial role in centriole assembly, spindle orientation, brain development, and ciliogenesis (4,17,27,35,41,64). Of clinical importance, patients with microcephaly and Seckel syndrome were found to have mutations in this gene (41,42).…”

Section: Discussionmentioning

confidence: 91%

Centrobin-mediated Regulation of the Centrosomal Protein 4.1-associated Protein (CPAP) Level Limits Centriole Length during Elongation Stage

Gudi

Haycraft

Bell

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background:The mechanism by which centriole dimensions are regulated is not understood. Results: The absence of centrobin leads to degradation of centrosomal protein 4.1-associated-protein (CPAP). High centrobin levels cause stabilization of CPAP and abnormal centrioles. Conclusion: Centrobin plays a role in the stability and centriole elongation function of CPAP and limits the centriole length. Significance: Identifying the regulatory mechanisms is crucial for understanding centriole biogenesis.

show abstract

“…It is known that the CPAP‐tubulin interaction is required for centriole and cilium elongation (Tang et al , 2009; Wu & Tang, 2012). Evidence comes from a functional study where a non‐tubulin‐binding CPAP variant results in a short cilium, suggesting that CPAPs' N‐terminal tubulin binding capability could determine cilium length (Wu & Tang, 2012). From this observation, we speculate that the Seckel variant CPAP (where a part of its CC5 domain is deleted) could have an altered tubulin binding activity possibly accounting for an elongated cilium.…”

Section: Discussionmentioning

confidence: 99%

CPAP promotes timely cilium disassembly to maintain neural progenitor pool

et al. 2016

View full text Add to dashboard Cite

A mutation in the centrosomal‐P4.1‐associated protein (CPAP) causes Seckel syndrome with microcephaly, which is suggested to arise from a decline in neural progenitor cells (NPCs) during development. However, mechanisms of NPCs maintenance remain unclear. Here, we report an unexpected role for the cilium in NPCs maintenance and identify CPAP as a negative regulator of ciliary length independent of its role in centrosome biogenesis. At the onset of cilium disassembly, CPAP provides a scaffold for the cilium disassembly complex (CDC), which includes Nde1, Aurora A, and OFD1, recruited to the ciliary base for timely cilium disassembly. In contrast, mutated CPAP fails to localize at the ciliary base associated with inefficient CDC recruitment, long cilia, retarded cilium disassembly, and delayed cell cycle re‐entry leading to premature differentiation of patient iPS‐derived NPCs. Aberrant CDC function also promotes premature differentiation of NPCs in Seckel iPS‐derived organoids. Thus, our results suggest a role for cilia in microcephaly and its involvement during neurogenesis and brain size control.

show abstract

CPAP is required for cilia formation in neuronal cells

Cited by 23 publications

References 28 publications

Genomic analysis of primordial dwarfism reveals novel disease genes

Genomic analysis of primordial dwarfism reveals novel disease genes

Centrobin-mediated Regulation of the Centrosomal Protein 4.1-associated Protein (CPAP) Level Limits Centriole Length during Elongation Stage

CPAP promotes timely cilium disassembly to maintain neural progenitor pool

Contact Info

Product

Resources

About