Dataset Information

PKA, PP1, and DC1 phosphorylation mediate alcohol-induced ciliary dysfunction in Chlamydomonas reinhardtii.

ABSTRACT: Excessive alcohol consumption impairs mucociliary clearance, in part, by compromising ciliary movement. Our previous study found alcohol reduces ciliary beat frequency in Chlamydomonas through a mechanism that involves the ? and ? heavy chains of the outer dynein arm (ODA). Moreover, we identified DC1, a subunit of the ODA-docking complex (ODA-DC), as the first ciliary target for alcohol. DC1 phosphorylation is alcohol sensitive and correlates with alcohol-induced ciliary dysfunction (AICD). Furthermore, DC1 phosphorylation is disrupted in the absence of the central pair and ODA. These results implicate a role for DC1 phosphorylation in regulating the ODA activity and mediating AICD. In our current study, we identified four alcohol-sensitive phosphosites in DC1: S33, T73, T351, and S628. Mutations of these sites rescue the assembly of the ODA-DC and ODA, resulting in wild-type swimming velocities. When cells were challenged with alcohol, we determined that three sites, S33, T351, and S628, are critical for mediating the ciliary slowing effects of alcohol. This result is consistent with our pharmacological studies, which reveal that both PP1 and PKA activities are required for AICD.

SUBMITTER: Yang F

PROVIDER: S-EPMC6226345 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Publications

PKA, PP1, and DC1 phosphorylation mediate alcohol-induced ciliary dysfunction in Chlamydomonas reinhardtii.

Yang Fan F Scarbrough Chasity C Sisson Joseph H JH Wirschell Maureen M

Alcohol (Fayetteville, N.Y.) 20180509

Excessive alcohol consumption impairs mucociliary clearance, in part, by compromising ciliary movement. Our previous study found alcohol reduces ciliary beat frequency in Chlamydomonas through a mechanism that involves the β and γ heavy chains of the outer dynein arm (ODA). Moreover, we identified DC1, a subunit of the ODA-docking complex (ODA-DC), as the first ciliary target for alcohol. DC1 phosphorylation is alcohol sensitive and correlates with alcohol-induced ciliary dysfunction (AICD). Fur ...[more]

PMID: 30336351

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Project description:Protein phosphorylation, which is one of the most important post-translational modifications (PTMs), is involved in regulating myriad cellular processes. Herein, we present a novel deep learning based approach for organism-specific protein phosphorylation site prediction in Chlamydomonas reinhardtii, a model algal phototroph. An ensemble model combining convolutional neural networks and long short-term memory (LSTM) achieves the best performance in predicting phosphorylation sites in C. reinhardtii. Deemed Chlamy-EnPhosSite, the measured best AUC and MCC are 0.90 and 0.64 respectively for a combined dataset of serine (S) and threonine (T) in independent testing higher than those measures for other predictors. When applied to the entire C. reinhardtii proteome (totaling 1,809,304 S and T sites), Chlamy-EnPhosSite yielded 499,411 phosphorylated sites with a cut-off value of 0.5 and 237,949 phosphorylated sites with a cut-off value of 0.7. These predictions were compared to an experimental dataset of phosphosites identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a blinded study and approximately 89.69% of 2,663 C. reinhardtii S and T phosphorylation sites were successfully predicted by Chlamy-EnPhosSite at a probability cut-off of 0.5 and 76.83% of sites were successfully identified at a more stringent 0.7 cut-off. Interestingly, Chlamy-EnPhosSite also successfully predicted experimentally confirmed phosphorylation sites in a protein sequence (e.g., RPS6 S245) which did not appear in the training dataset, highlighting prediction accuracy and the power of leveraging predictions to identify biologically relevant PTM sites. These results demonstrate that our method represents a robust and complementary technique for high-throughput phosphorylation site prediction in C. reinhardtii. It has potential to serve as a useful tool to the community. Chlamy-EnPhosSite will contribute to the understanding of how protein phosphorylation influences various biological processes in this important model microalga.

Dataset Information

PKA, PP1, and DC1 phosphorylation mediate alcohol-induced ciliary dysfunction in Chlamydomonas reinhardtii.

Publications

PKA, PP1, and DC1 phosphorylation mediate alcohol-induced ciliary dysfunction in Chlamydomonas reinhardtii.

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