Ethanol impairs microtubule formation via interactions at a microtubule associated protein-sensitive site.

TitleEthanol impairs microtubule formation via interactions at a microtubule associated protein-sensitive site.
Publication TypeJournal Article
Year of Publication2013
JournalAlcohol (Fayetteville, N.Y.)
Volume47
Issue7
Pagination539-43
ISSN0741-8329
Abstract

Prolonged ethanol abuse has been associated with brain injury caused by impaired synaptogenesis, cellular migration, neurogenesis, and cell signaling, all of which require proper microtubule functioning. However, the means by which ethanol may impair microtubule formation or function and the role that microtubule-associated proteins (MAPs) have in mediating such effects are not clear. In the present studies, purified MAP-deficient (2 mg/mL) and MAP-rich (pre-conjugated; 1 mg/mL) bovine α/β tubulin dimer was allowed to polymerize at 37 °C, forming microtubules in the presence or absence of ethanol (25-500 mM). Microtubule formation was assessed in a 96-well format using a turbidity assay, with absorption measured at 340 nm for 45 min. Additional studies co-exposed α/β tubulin dimers to 50 mM ethanol and purified MAPs (0.1 mg/mL) for 45 min. Polymerization of MAP-deficient tubulin was significantly decreased (at 15-45 min of polymerization) during exposure to ethanol (>25 mM). In contrast, ethanol exposure did not alter polymerization of α/β tubulin dimers pre-conjugated to MAPs, at any concentration. Concurrent exposure of MAP-deficient tubulin with purified MAPs and ethanol resulted in significant and time-dependent decreases in tubulin polymerization, with recovery from inhibition at later time points. The present results suggest that ethanol disrupts MAP-independent microtubule formation and MAP-dependent microtubule formation via direct actions at an MAP-sensitive microtubule residue, indicating that disruption of neuronal microtubule formation and function may contribute to the neurodegenerative effects of binge-like ethanol intake.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S0741-8329(13)00113-4
DOI10.1016/j.alcohol.2013.08.001
Short TitleAlcohol
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