The regulatory subunit of adenylate cyclase interacts with cytoskeletal components

Abstract

The adenylate cyclase system, which mediates cellular responses to a variety of hormones and neurotransmitters, contains at least three plasma membrane-associated proteins: the hormone receptor, the regulatory or guanyl nucleotide-binding unit (G unit) and the catalytic moiety. Activation of the enzyme after binding of hormone to the receptor involves binding of GTP to the G unit¹. Activation can be enhanced by increasing the fluidity of the membrane with unsaturated fatty acids² with the local anaesthetic prilocaine³, and perhaps, in vivo, by phospholipid methylation⁴. Disruption of microtubules increases localized mobility of membrane proteins in a manner similar to that of unsaturated fatty acids⁵ and can enhance cyclic AMP accumulation in intact leukocytes^6–9. We therefore decided to investigate whether there is a direct interaction between micro-tubules and adenylate cyclase. We show here that colchicine, vinblastine and cis- unsaturated fatty acids enhance G unit-mediated activation of adenylate cyclase, implying that microtubules or tubulin are involved in the attachment of the G unit to the membrane.