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

Fan Yang, Chasity Scarbrough, Joseph Harold Sisson, Maureen Wirschell

Research output: Contribution to journalArticle

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 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). 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.

LanguageEnglish (US)
Pages31-38
Number of pages8
JournalAlcohol
Volume75
DOIs
StatePublished - Mar 1 2019

Fingerprint

Chlamydomonas reinhardtii
Phosphorylation
Dyneins
alcohol
Alcohols
Chlamydomonas
Mucociliary Clearance
alcohol consumption
Alcohol Drinking
Pharmacology
Mutation

Keywords

  • Alcohol
  • Cilia
  • Dynein
  • Motility

ASJC Scopus subject areas

  • Health(social science)
  • Biochemistry
  • Toxicology
  • Neurology
  • Behavioral Neuroscience

Cite this

PKA, PP1, and DC1 phosphorylation mediate alcohol-induced ciliary dysfunction in Chlamydomonas reinhardtii. / Yang, Fan; Scarbrough, Chasity; Sisson, Joseph Harold; Wirschell, Maureen.

In: Alcohol, Vol. 75, 01.03.2019, p. 31-38.

Research output: Contribution to journalArticle

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