I. Karakesisoglou et al., An epidermal plakin that integrates actin and microtubule networks at cellular junctions, J CELL BIOL, 149(1), 2000, pp. 195-208
Plakins are cytoskeletal linker proteins initially thought to interact excl
usively with intermediate filaments (IFs), but recently were found to assoc
iate additionally with actin and microtubule networks. Here, we report on A
CF7, a mammalian orthologue of the Drosophila kakapo plakin genetically inv
olved in epidermal-muscle adhesion and neuromuscular junctions. While ACF7/
kakapo is divergent from other plakins in its IF-binding domain, it has at
least one actin (K-d = 0.35 mu M) and one microtubule (K-d similar to 6 mu
M) binding domain. Similar to its fly counterpart, ACF7 is expressed in the
epidermis. In well spread epidermal keratinocytes, ACF7 discontinuously de
corates the cytoskeleton at the cell periphery, including microtubules (MTs
) and actin filaments (AFs) that are aligned in parallel converging at foca
l contacts. Upon calcium induction of intercellular adhesion, ACF7 and the
cytoskeleton reorganize at cell-cell borders but with different kinetics fr
om adherens junctions and desmosomes. Treatments with cytoskeletal depolyme
rizing drugs reveal that ACF7's cytoskeletal association is dependent upon
the microtubule network, but ACF7 also appears to stabilize actin at. sites
where microtubules and microfilaments meet. We posit that ACM may function
in microtubule dynamics to facilitate actin-microtubule interactions at th
e cell periphery and to couple the microtubule network to cellular junction
s. These attributes provide a clear explanation for the kakapo mutant pheno
type in flies.