Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth

Sharma, Ashwani; Aher, Amol; Dynes, Nicola J.; Frey, Daniel; Katrukha, Eugene A.; Jaussi, Rolf; Grigoriev, Ilya; Croisier, Marie; Kammerer, Richard A.; Akhmanova, Anna; Gönczy, Pierre; Steinmetz, Michel O.

doi:10.1016/j.devcel.2016.04.024

Cited by 94 publications

(131 citation statements)

References 52 publications

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“…Concentrations of stock solutions varied between ~50–250 nM for full-length KIF21B-GFP, KIF21B-FLΔrCC-GFP and KIF21B-MD-CCΔrCC-GFP, and 0.6–1.2 µM for MD-CC1-GFP and GFP-L-WD40. Strep-tag-based KIF5B-560-GFP protein purification from HEK293T cells was done using Strep(II)-streptactin affinity purification method (Sharma et al, 2016). …”

Section: Methodsmentioning

confidence: 99%

Kinesin-4 KIF21B is a potent microtubule pausing factor

Riel

Rai

Bianchi

et al. 2017

eLife

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Microtubules are dynamic polymers that in cells can grow, shrink or pause, but the factors that promote pausing are poorly understood. Here, we show that the mammalian kinesin-4 KIF21B is a processive motor that can accumulate at microtubule plus ends and induce pausing. A few KIF21B molecules are sufficient to induce strong growth inhibition of a microtubule plus end in vitro. This property depends on non-motor microtubule-binding domains located in the stalk region and the C-terminal WD40 domain. The WD40-containing KIF21B tail displays preference for a GTP-type over a GDP-type microtubule lattice and contributes to the interaction of KIF21B with microtubule plus ends. KIF21B also contains a motor-inhibiting domain that does not fully block the interaction of the protein with microtubules, but rather enhances its pause-inducing activity by preventing KIF21B detachment from microtubule tips. Thus, KIF21B combines microtubule-binding and regulatory activities that together constitute an autonomous microtubule pausing factor.DOI: http://dx.doi.org/10.7554/eLife.24746.001

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Section: Methodsmentioning

confidence: 99%

Kinesin-4 KIF21B is a potent microtubule pausing factor

Riel

Rai

Bianchi

et al. 2017

eLife

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“…The same results have been observed for depletion of the end-capping protein CP110, which normally localizes to the distal tips of both parental and daughter centrioles [Kleylein-Sohn et al, 2007;Schmidt et al, 2009]. Recently, more insight into the regulation of centriole length was gained with the identification of the N-terminal LID element of CPAP/CENPJ, which acts as a cap that sterically blocks tubulin addition to the centriole distal end, thus controlling this organelle size and ensuring the exceptionally slow growth rate of centriolar microtubules compared to their cytoplasmic counterparts [Sharma et al, 2016].…”

Section: Discussionmentioning

confidence: 99%

Novel STIL Compound Heterozygous Mutations Cause Severe Fetal Microcephaly and Centriolar Lengthening

Cristofoli

Keersmaecker²,

Catte³

et al. 2017

Mol Syndromol

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STIL (SCL/TAL1 interrupting locus) is a core component of the centriole duplication process. <i>STIL</i> mutations have been associated with both autosomal recessive primary microcephaly (MCPH) and holoprosencephaly. In this report, we describe a family with multiple miscarriages and 2 terminations of pregnancy due to marked fetal microcephaly, delayed cortical gyrification, and dysgenesis of the corpus callosum. Whole exome sequencing allowed us to identify novel compound heterozygous mutations in <i>STIL.</i> The mutations lie, respectively, in the CPAP/CENPJ and the hsSAS6 interacting domains of STIL. M-phase synchronized amniocytes from both affected fetuses did not display an aberrant number of centrioles, as shown previously for either STIL-depleted or overexpressing cells. However, we observed an elongation of at least 1 centriole for each duplicated centrosome. These preliminary results may point to a novel mechanism causing MCPH and embryonic lethality in humans.

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“…The exact role of CEP135 in cartwheel formation in vertebrates therefore remains unclear and no homolog of Bld10p has been identified in Caenorhabditis elegans . Finally, the deposition of microtubules onto the cartwheel clearly requires CPAP ( C entrosomal P 4.1- A ssociated P rotein)/hSAS-4) 3738,39 .…”

Section: Centrosome Structure and Assemblymentioning

confidence: 99%

Once and only once: mechanisms of centriole duplication and their deregulation in disease

Nigg

Holland

2018

Nat Rev Mol Cell Biol

407

546

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Centrioles are conserved microtubule-based organelles that form the core of the centrosome and act as templates for the formation of cilia and flagella. Centrioles have important roles in most microtubule related processes, including motility, cell division and cell signaling. To coordinate these diverse cellular processes, centriole number must be tightly controlled. In cycling cells, one new centriole is formed next to each preexisting centriole in every cell cycle. Advances in imaging, proteomics, structural biology and genome editing have revealed new insights into centriole biogenesis, how centriole numbers are controlled and how alterations in these structures contribute to diseases such as cancer and neurodevelopmental disorders. Moreover, recent work has uncovered the existence of surveillance pathways that limit proliferation of cells with numerical centriole aberrations. Here we discuss recent progress in this field with a focus on signaling pathways and molecular mechanisms.

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Centriolar CPAP/SAS-4 Imparts Slow Processive Microtubule Growth

Cited by 94 publications

References 52 publications

Kinesin-4 KIF21B is a potent microtubule pausing factor

Kinesin-4 KIF21B is a potent microtubule pausing factor

Novel STIL Compound Heterozygous Mutations Cause Severe Fetal Microcephaly and Centriolar Lengthening

Once and only once: mechanisms of centriole duplication and their deregulation in disease

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