Nutritional stress-induced regulation of microtubule organization and mRNP transport by HDAC1 controlled α-tubulin acetylation

Communications Biology · 4 authors, 4 centres

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TL;DR

In the Drosophila female germline, nutritional stress-induced phosphorylation of HDAC1 reduces its ability to deacetylate α-tubulin, leading to microtubule hyperacetylation, loss of cytoplasmic microtubules, and aggregation of mRNPs into P-bodies.

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This preclinical study used Drosophila melanogaster female germline to investigate how nutritional stress regulates microtubule dynamics and mRNP transport via HDAC1-mediated α-tubulin K40 acetylation. The authors found that starvation induces hyperacetylation of α-tubulin, depleting microtubules from the cytoplasm and triggering P-body formation and oogenesis arrest. HDAC1 RNAi depletion phenocopied nutritional stress, and in vitro assays confirmed HDAC1 directly deacetylates α-tubulin. Quantitative phosphoproteomics identified HDAC1 phosphorylation at S391 as significantly increased under nutritional stress, and a phospho-mimetic mutant (S391D) showed substantially reduced deacetylation of α-tubulin compared to wild-type HDAC1. Limitations include that the upstream kinase responsible for S391 phosphorylation remains unidentified, as CK2 inhibition did not affect the starvation-induced response, and human relevance is indirect.

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other

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preclinical research

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AI pipeline

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ORIGINAL PAPER

PMC10368696

Nutritional stress-induced regulation of microtubule organization and mRNP transport by HDAC1 controlled α-tubulin acetylation

Communications Biology

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ABSTRACT

In response to nutritional stress, microtubules in cells of the Drosophila female germline are depleted from the cytoplasm and accumulate cortically. This triggers aggregation of mRNPs into large processing bodies (P-bodies) and oogenesis arrest. Here, we show that hyperacetylation of α-tubulin at lysine 40 (K40) alters microtubule dynamics and P-body formation. We found that depletion of histone deacetylase 1 (HDAC1) by RNAi phenocopies the nutritional stress response, causing α-tubulin hyperacetylation and accumulation of maternally deposited mRNPs in P-bodies. Through in vitro and in vivo studies, we identify HDAC1 as a direct regulator of α-tubulin K40 acetylation status. In well-fed flies, HDAC1 maintains low levels of α-tubulin acetylation, enabling the microtubule dynamics required for mRNP transport. Using quantitative phosphoproteomics we identify nutritional stress-induced changes in protein phosphorylation that act upstream of α-tubulin acetylation, including phosphorylation of HDAC1 at S391, which reduces its ability to deacetylate α-tubulin. These results reveal that Drosophila HDAC1 senses and relays the nutritional status, which regulates germline development through modulation of cytoskeleton dynamics.

CITATION EXPORT

Frank Wippich, Vaishali, Marco L. Hennrich et al.. Nutritional stress-induced regulation of microtubule organization and mRNP transport by HDAC1 controlled α-tubulin acetylation. Communications Biology. (2023). https://doi.org/10.1038/s42003-023-05138-w

AUTHORS

4 · 4 CENTRES

Frank Wippich, Vaishali, Marco L. Hennrich, Anne Ephrussi

1grid.4709.a0000 0004 0495 846XDevelopmental Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, Heidelberg, 69117 Germany
2grid.4709.a0000 0004 0495 846XStructural and Computational Biology Unit, European Molecular Biology Laboratory (EMBL) Heidelberg, Meyerhofstrasse 1, Heidelberg, 69117 Germany
3grid.420105.20000 0004 0609 8483Present Address: Cellzome GmbH, GlaxoSmithKline, Heidelberg, Germany
4grid.83440.3b0000000121901201Present Address: Department of Cell and Developmental Biology, University College London, Gower Street, London, WC1E 6BT UK