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Vol. 11, Issue 10, 3573-3587, October 2000
Department of Cell Biology, The Scripps Research Institute, La
Jolla, California 92037
Microtubule-associated protein 2 (MAP2) is a neuronal
phosphoprotein that promotes net microtubule growth and actin
cross-linking and bundling in vitro. Little is known about MAP2
regulation or its interaction with the cytoskeleton in vivo. Here we
investigate the in vivo function of three specific sites of
phosphorylation on MAP2. cAMP-dependent protein kinase activity
disrupts the MAP2-microtubule interaction in living HeLa cells and
promotes MAP2c localization to peripheral membrane ruffles enriched in
actin. cAMP-dependent protein kinase phosphorylates serines within
three KXGS motifs, one within each tubulin-binding repeat. These highly
conserved motifs are also found in homologous proteins tau and
MAP4. Phosphorylation at two of these sites was detected in brain
tissue. Constitutive phosphorylation at these sites was mimicked by
single, double, and triple mutations to glutamic acid. Biochemical and
microscopy-based assays indicated that mutation of a single residue was
adequate to disrupt the MAP2-microtubule interaction in HeLa cells.
Double or triple point mutation promoted MAP2c localization to the
actin cytoskeleton. Specific association between MAP2c and the actin cytoskeleton was demonstrated by retention of MAP2c-actin
colocalization after detergent extraction. Specific phosphorylation
states may enhance the interaction of MAP2 with the actin cytoskeleton,
thereby providing a regulated mechanism for MAP2 function within
distinct cytoskeletal domains.
Online version of this article contains video
material. Online verson available at www.molbiolcell.org.
*
Corresponding author: E-mail address:
shelley{at}scripps.edu.
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