Two Polo-like kinase 4 binding domains in Asterless perform distinct roles in regulating kinase stability

Klebba, Joseph E.; Galletta, Brian J.; Nye, Jonathan; Plevock, Karen M.; Buster, Daniel W.; Hollingsworth, Natalie A; Slep, Kevin C.; Rusan, Nasser M.; Rogers, Gerald S.

doi:10.1083/jcb.201410105

Cited by 31 publications

(59 citation statements)

References 43 publications

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“…In dividing cells, Asl serves as a receptor recruiting Plk4 to the centriole for centriole duplication [24, 27, 30, 31]. However, Asl’s interaction with Plk4 is complex and mediated via two distinct domains (Asl C-terminus and N-terminus), which have distinct functions during centriole duplication [22]. Here, we show that Plk4’sN-terminus regulates Asl attachment to the centriole during spermiogenesis.…”

Section: Resultsmentioning

confidence: 89%

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Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila

et al. 2015

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SUMMARY Centrosome reduction is the decrease in centrosomal components during spermatid differentiation (spermiogenesis) [1, 2]. It is one of several dramatic subcellular reorganizations that leads to spermatozoa formation common to a wide range of animals [3]. However, the mechanism underlying centrosome reduction is unknown and its functions are unclear. Here, we show that in Drosophila melanogaster spermiogenesis, the quantity of centrosomal proteins is dramatically reduced [4, 5];for example, Asterless (Asl) is reduced ~500-fold and is barely detected in spermatozoa. Asl reduction is regulated through a subset of its domains by the master regulator of centriole duplication Plk4[6–8] and by the ubiquitin ligase that targets Plk4 for degradation: Slimb [9, 10]. When Asl reduction is attenuated by Asl overexpression, plk4 mutations, Plk4 RNAi, or Slimb overexpression, Asl levels are higher in spermatozoa, resulting in embryo’s with reduced viability. Significantly, overexpressing Plk4 and Asl simultaneously, or combining plk4 and slimb mutations, balances their opposing effects on Asl reduction, restoring seemingly normal fertility. This suggests that increased Asl levels cause the observed reduced fertility, and not other pleotropic effects. Attenuation of Asl reduction also causes delayed development and a failure to form astral microtubules in the zygote. Together, we provide the first insight into a molecular mechanism that regulates centrosome reduction and the first direct evidence that centrosome reduction is essential for postfertilization development.

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Section: Resultsmentioning

confidence: 89%

“…Asl’s domain 1 interact with Polo-like kinase 4 (Plk4)[6–8, 22], the master regulator of centriole formation. Like Asl, Plk4 is reduced during spermiogenesis (Fig.…”

Section: Resultsmentioning

confidence: 99%

Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila

et al. 2015

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“…[53]). PBs 1 and 2 of PLK4 (formerly named cryptic PBs) are important for dimerization and centriole recruitment of PLK4 [54–59]. Dimerization of PLK4 and trans-autophosphorylation is important for both activation of the kinase and regulation of PLK4 levels.…”

Section: A Core Module For Centriole Duplicationmentioning

confidence: 99%

The PLK4–STIL–SAS-6 module at the core of centriole duplication

Arquint

Nigg

2016

Biochemical Society Transactions

131

138

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Centrioles are microtubule-based core components of centrosomes and cilia. They are duplicated exactly once during S-phase progression. Central to formation of each new (daughter) centriole is the formation of a nine-fold symmetrical cartwheel structure onto which microtubule triplets are deposited. In recent years, a module comprising the protein kinase polo-like kinase 4 (PLK4) and the two proteins STIL and SAS-6 have been shown to stay at the core of centriole duplication. Depletion of any one of these three proteins blocks centriole duplication and, conversely, overexpression causes centriole amplification. In this short review article, we summarize recent insights into how PLK4, STIL and SAS-6 co-operate in space and time to form a new centriole. These advances begin to shed light on the very first steps of centriole biogenesis.

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“…The asterless then recruits protein Plk4 ("polo-like kinase four") to form a base and govern the construction of a new centriole [85]. Plk4 is also known as (aka) "SAK".…”

Section: Preliminary Considerations: Review Of Centriole Duplication mentioning

confidence: 99%

A Review of Electromagnetic Activity in Cellular Mechanics

Huston¹

2016

ABB

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This is a review of recent literature concerning electromagnetic effects on cellular mechanics. "Recent" refers primarily to papers published in this (the 21 st ) century. The review shows that there are relatively few papers on cellular electromagnetics as compared with those on proteins, biochemistry, and cellular anatomy. The principal finding of the reviewed papers is that cellular electromagnetic fields appear to arise from longitudinal vibrations of the filaments making up the walls of the microtubules. Microtubules are long hollow cylinders which form the overall structure of the centrioles. The microtubules, and therefore the centrioles themselves, are arranged in nine sets of parallel blades with each blade having three microtubules. The centrioles occur in pairs perpendicularly to each other. During mitosis (cell division) the centriole pair becomes two pair which then separate and divide the cell into two. It seems that electromagnetic forces play a central role in this division. Electromagnetic activity in wound healing and in the imaging and treatment of tumors is discussed.

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Two Polo-like kinase 4 binding domains in Asterless perform distinct roles in regulating kinase stability

Abstract: The Asterless N terminus promotes Plk4 homodimerization and autophosphorylation during interphase, whereas its C terminus stabilizes Plk4 during mitosis.

Cited by 31 publications

References 43 publications

Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila

Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila

The PLK4–STIL–SAS-6 module at the core of centriole duplication

A Review of Electromagnetic Activity in Cellular Mechanics

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