An anchoring factor targets protein phosphatase 2A to brain microtubules

Protein phosphatase 2A (PP2A) is a ubiquitously expressed serine/threonine phosphatase composed of a heterodimeric core enzyme that associates with a variety of regulatory subunits. A fraction of brain PP2A associates with mi crotubules and may play a role in regulating phosphorylation of microtubule -associated proteins. We examined the isoform specificity and the mechanism involved in the association of PP2A with brain microtubules. Only the R2 a lpha (B/PR55 alpha) and R2 beta (B/PR55 beta) regulatory subunits associate d with endogenous neural microtubules. Neither the R2 gamma (B/PR55 gamma) nor members of the R5 (B'/PR56) family of regulatory subunits co-sedimented with microtubules, although abundant amounts of these proteins were detect ed in brain. The efficient association of PP2A with microtubules in vitro w as dependent on an anchoring activity present in a brain protein fraction c ontaining microtubule-associated and microtubule-interacting proteins. Anch oring factor-dependent association of PP2A with microtubules was specific f or the heterotrimeric form of PP2A. The core dimer and the isolated subunit s of PP2A had very little affinity for microtubules. Characterization of a fraction enriched in the anchoring factor showed that the activity was a he ar labile protein that does not correspond to classical microtubule-associa ted proteins. The anchoring factor associated with microtubules independent ly of PP2A. These results indicate the association of PP2A with microtubule s can be mediated by an anchoring factor that interacts in an isoform-speci fic manner with heterotrimeric forms of the phosphatase. (C) 1999 Elsevier Science B.V. All rights reserved.