<i>Drosophila</i> Sas-6, Ana2 and Sas-4 self-organise into macromolecular structures that can be used to probe centriole and centrosome assembly

Gartenmann, Lisa; Vicente, Catarina; Wainman, Alan; Novak, Zsofi A.; Sieber, Boris; Richens, Jennifer H.; Raff, Jordan W.

doi:10.1242/jcs.244574

Cited by 17 publications

(29 citation statements)

References 89 publications

(142 reference statements)

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“…CEP152 encodes a protein with several coiled-coil domains that is localized at the centrosome [ 84 , 85 , 86 ]. Mutations in CEP152 are a rare cause of MCPH; however, they are a frequent cause of Seckel syndrome [ 16 , 84 , 85 ].…”

Section: Mcph Genesmentioning

confidence: 99%

“…SASS6 encodes a protein with a coiled-coil domain that is expressed in the cells from G2 until mitosis [ 107 , 108 ]. At the onset of centriole duplication, SASS6 is recruited to the centriole and acts as a scaffolding component and during centriole biogenesis it interacts with several proteins [ 80 , 86 , 87 , 109 , 110 ]; overexpression of SASS6 leads to centrosome duplication [ 111 , 112 ].…”

Section: Mcph Genesmentioning

confidence: 99%

“…CEP152–CEP63 interaction triggers the engagement of the kinase Plk-4, which autophosphorylates and subsequently phosphorylates STIL, which in turn recruits SASS6 [ 155 , 156 , 157 , 158 , 159 ]. SASS6 and STIL oligomerize and form the core of the daughter centriole, engaging two other MCPH proteins, CEP135 and CENPJ, essential for microtubule nucleation and lengthening of the centriole [ 86 , 108 , 155 , 156 , 160 , 161 ]. ASPM and WDR62 are also localized at the pericentriolar material where other proteins, for instance CDK5RAP2 and pericentrin, are recruited, and microtubules start assembling, as the daughter centriole is forming [ 30 , 162 , 163 ].…”

Section: Cellular Processes and Molecular Pathways In Mcphmentioning

confidence: 99%

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Molecular Genetics of Microcephaly Primary Hereditary: An Overview

et al. 2021

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MicroCephaly Primary Hereditary (MCPH) is a rare congenital neurodevelopmental disorder characterized by a significant reduction of the occipitofrontal head circumference and mild to moderate mental disability. Patients have small brains, though with overall normal architecture; therefore, studying MCPH can reveal not only the pathological mechanisms leading to this condition, but also the mechanisms operating during normal development. MCPH is genetically heterogeneous, with 27 genes listed so far in the Online Mendelian Inheritance in Man (OMIM) database. In this review, we discuss the role of MCPH proteins and delineate the molecular mechanisms and common pathways in which they participate.

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Section: Mcph Genesmentioning

confidence: 99%

Section: Mcph Genesmentioning

confidence: 99%

Section: Cellular Processes and Molecular Pathways In Mcphmentioning

confidence: 99%

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Molecular Genetics of Microcephaly Primary Hereditary: An Overview

et al. 2021

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“…Embryos were collected for 1 h, aged for 1 h, and processed as described (Gartenmann et al, 2020). Testes from adult male flies expressing either WT or S34T Ana1-GFP constructs in an ana1 -/- background were dissected, fixed and stained, as described previously (Roque et al, 2012).…”

Section: Methodsmentioning

confidence: 99%

Ana1 recruits PLK1 to mother centrioles to promote mitotic PCM assembly and centriole elongation

Alvarez‐Rodrigo

Wainman

Raff

2020

Preprint

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Polo kinase (PLK1) is a master cell cycle regulator that is recruited to various subcellular structures by its Polo-Box domain (PBD), which binds to phosphorylated S-pS/pT motifs. Polo has multiple functions at centrioles and centrosomes, and we previously showed that phosphorylated Sas-4 initiates Polo recruitment to newly formed centrioles, while phosphorylated Spd-2 recruits Polo to the mitotic Pericentriolar Material (PCM) that assembles around mother centrioles. Here, we investigate whether additional proteins recruit Polo to centrioles and/or centrosomes, and find that Ana1 (Cep295 in mammals) helps recruit Polo to mother centrioles. If this function is impaired, mother centrioles can still duplicate and disengage from their daughters, but they can no longer efficiently assemble a mitotic PCM or elongate their centrioles in G2. Thus, Ana1 is part of a sequential phosphorylation cascade that recruits Polo to centrioles to drive mitotic centrosome assembly and centriole elongation in G2, but not centriole duplication or disengagement.

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“…Each centrosome is composed of a pair of centrioles surrounded by pericentriolar material (PCM) proteins. Centriolar proteins Spindle assembly abnormal 4 (Sas-4), Anastral spindle 2 (Ana2), and Asl are essential for centriole biogenesis and assembly (Varmark, Llamazares et al 2007, Dzhindzhev, Yu et al 2010, Wang, Li et al 2011, Novak, Wainman et al 2016, Gartenmann, Vicente et al 2020. In control interphase and metaphase NSCs, Sas-4 was always observed at the centrosomes overlapping with Asl (Figure S3B-C).…”

Section: Hyx Is Required For Centrosome Assembly In Dividing Nscsmentioning

confidence: 99%

Tumour Suppressor Parafibromin/Hyrax Governs Cell Polarity and Centrosome Assembly in Neural Stem Cells

Deng

Wang

et al. 2021

Preprint

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Neural stem cells (NSCs) divide asymmetrically to balance their self-renewal and differentiation. The imbalance can lead to NSC overgrowth and tumour formation. The function of Parafibromin, a conserved tumour suppressor, in the nervous system is not established. Here, we demonstrate that Drosophila Parafibromin/Hyrax (Hyx) inhibits NSC overgrowth by governing the cell polarity. Hyx is essential for the apicobasal polarity by localizing both apical and basal proteins asymmetrically in NSCs. hyx loss results in the symmetric division of NSCs, leading to the formation of supernumerary NSCs in the larval brain. Human Parafibromin fully rescues NSC overgrowth and cell polarity defects in Drosophila hyx mutant brains. Hyx plays a novel role in maintaining interphase microtubule-organizing center and mitotic spindle formation in NSCs. Hyx is required for the proper localization of a key centrosomal protein Polo and microtubule-binding proteins Msps and D-TACC in dividing NSCs. This study discovers that Hyx has a brain tumour suppressor-like function and maintains NSC polarity by regulating centrosome function and microtubule growth. The new paradigm that Parafibromin orchestrates cell polarity and centrosomal assembly may be relevant to Parafibromin/HRPT2-associated cancers.

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Drosophila Sas-6, Ana2 and Sas-4 self-organise into macromolecular structures that can be used to probe centriole and centrosome assembly

Abstract: Sas-6, Ana2 and Sas-4 self-organise into macromolecular structures that can be used to probe centriole/centrosome assembly

Cited by 17 publications

References 89 publications

Molecular Genetics of Microcephaly Primary Hereditary: An Overview

Molecular Genetics of Microcephaly Primary Hereditary: An Overview

Ana1 recruits PLK1 to mother centrioles to promote mitotic PCM assembly and centriole elongation

Tumour Suppressor Parafibromin/Hyrax Governs Cell Polarity and Centrosome Assembly in Neural Stem Cells

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