An epidermal plakin that integrates actin and microtubule networks at cellular junctions

Citation
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
Citations number
60
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
00219525 → ACNP
Volume
149
Issue
1
Year of publication
2000
Pages
195 - 208
Database
ISI
SICI code
0021-9525(20000403)149:1<195:AEPTIA>2.0.ZU;2-Y
Abstract
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.