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dMARCH8, a Drosophila ubiquitin E3 ligase, regulates polymodifications of tubulin in the spermiogenic pathway

Ujwala A. S. Gosavi, Nabanita Chatterjee, Utsav Nyachhyon, Brian R Pearce, Robert J Harvey, Christopher Bazinet
doi: https://doi.org/10.1101/112243
Ujwala A. S. Gosavi
1Department of Biological Sciences, St. John’s University, Jamaica, New York 11439, USA
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Nabanita Chatterjee
1Department of Biological Sciences, St. John’s University, Jamaica, New York 11439, USA
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Utsav Nyachhyon
1Department of Biological Sciences, St. John’s University, Jamaica, New York 11439, USA
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Brian R Pearce
2Department of Pharmacology, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK
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Robert J Harvey
2Department of Pharmacology, UCL School of Pharmacy, 29-39 Brunswick Square, London WC1N 1AX, UK
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Christopher Bazinet
1Department of Biological Sciences, St. John’s University, Jamaica, New York 11439, USA
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ABSTRACT

Ciliary stability and function are regulated by the covalent addition of polyglutamate and polyglycine chains to axonemal tubulin subunits. The Drosophila gene CG13442 encodes a predicted ubiquitin E3 ligase involved in the regulation of tubulin glycylation and glutamylation. Homologous to mammalian MARCH8, CG13442/dMARCH8 is required for male fertility. Sperm in dMARCH8 mutant testes appear to undergo a normal individualization process but fail to be transferred to the seminal vesicle. This phenotype is very similar to that of mutants in the Ntl gene, shown here to be a glycine transporter using a [3H]glycine uptake assay. Mutations in dMARCH8 are associated with a reduction of both polyglutamylation and polyglycylation of sperm tubulin. Polyglutamylation of tubulin is significantly increased in the Ntl− background, and recovers to wild-type levels in the Ntl−-dMARCH8− double mutant background, indicating that glycine and glutamate compete for some common site(s) on tubulin molecules in this system. By analogy to the regulation of the mammalian glycine transporter GlyT2 through ubiquitin-mediated trafficking between the plasma membrane and endosome, dMARCH8 may target Ntl and glutamate transporters, or other upstream regulators of these proteins.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted February 27, 2017.
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dMARCH8, a Drosophila ubiquitin E3 ligase, regulates polymodifications of tubulin in the spermiogenic pathway
Ujwala A. S. Gosavi, Nabanita Chatterjee, Utsav Nyachhyon, Brian R Pearce, Robert J Harvey, Christopher Bazinet
bioRxiv 112243; doi: https://doi.org/10.1101/112243
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dMARCH8, a Drosophila ubiquitin E3 ligase, regulates polymodifications of tubulin in the spermiogenic pathway
Ujwala A. S. Gosavi, Nabanita Chatterjee, Utsav Nyachhyon, Brian R Pearce, Robert J Harvey, Christopher Bazinet
bioRxiv 112243; doi: https://doi.org/10.1101/112243

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